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Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome that has come back or has not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Interferon gamma-1b may boost the immune system activity. Giving pembrolizumab and interferon gamma-1b together may work better in treating patients with stage IB-IVB mycosis fungoides and sezary syndrome.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Interferon Gamma-1b
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
   least one standard systemic therapy; maximal stage since diagnosis will determine
   eligibility; current disease stage at time of entry will also be documented but will
   not be used for eligibility

   - Subjects must have the following minimum wash-out from previous treatments and without
   treatment between documentation of relapse/progression and enrollment:

      - >= 2 weeks for local radiation therapy

      - >= 8 weeks for low dose (12 Gy or less) total skin electron beam therapy (TSEBT)

      - >= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational
      agents that are not defined as immunotherapy, or for tumor-targeting monoclonal
      antibodies (mAbs) with the exception of alemtuzumab for which the washout is at
      least 16 weeks

      - >= 15 weeks for anti-CD137 or anti-CTLA-4 (including ipilimumab or any other
      antibody or drug specifically targeting T-cell co-stimulation or checkpoint
      pathways)

      - >= 2 weeks from resolution (i.e., < grade 1 or at baseline) from adverse event
      (AE)s due to procedures performed or therapeutic agents administered

      - >= 2 weeks for retinoids, interferons, vorinostat, romidepsin and denileukin
      diftitox

      - >= 4 weeks for doses of systemic corticosteroidsgreater than 10 mg/day of
      prednisone or equivalent; patients who are on physiologic doses of
      corticosteroids (prednisone equivalent 10 mg/day or less) may participate,
      however, they must be on a stable dose for at least 4 weeks before enrollment;
      patients who are on low or moderate potency topical corticosteroids may
      participate if they are on a stable dose for at least 4 weeks before enrollment;
      inhaled corticosteroids are acceptable; local injections of corticosteroids are
      acceptable; all corticosteroids will be reported as concomitant medications

      - >= 2 weeks for phototherapy

      - >= 1 week for topical therapy (including retinoid, nitrogen mustard, or
      imiquimod)

   - Patients with prior treatment with IFN-gamma will be eligible, if they previously
   tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three
   weeks before initiation of therapy on this trial

   - Have measurable disease based on modified severity-weighted assessment tool (mSWAT);
   tumor lesions situated in a previously irradiated area are considered measurable if
   progression has been demonstrated in such lesions

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >=
   1500/mcL

   - Performed within 10 days of treatment initiation: Platelets >= 100000/mcL

   - Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6
   mmol/L

   - Performed within 10 days of treatment initiation: Creatinine =< 1.5 x upper limit
   normal (ULN) OR

   - Performed within 10 days of treatment initiation: Measured or calculated creatinine
   clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN

      - Creatinine clearance (CrCl) should be calculated per institutional standard;
      glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

   - Performed within 10 days of treatment initiation: Total bilirubin =< 1.5 x ULN OR
   direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN

   - Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST)
   (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)
   (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients
   with liver metastases

   - Women of child-bearing potential and men must agree to use adequate contraception
   (hormonal or barrier method of birth control; abstinence) before to study entry and
   for the duration of study participation; female patients of childbearing potential
   must have a negative urine or serum pregnancy test within 72 hours before receiving
   the first dose of study medication; if the urine test is positive or cannot be
   confirmed as negative, a serum pregnancy test will be required; female patients of
   childbearing potential must be willing to use an adequate method of contraception for
   the course of the study through 120 days after the last dose of study medication;
   Note: abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the patient; male patients of reproductive potential must agree to
   use an adequate method of contraception starting with the first dose of study therapy
   through 120 days after the last dose of study therapy; Note: abstinence is acceptable
   if this is the usual lifestyle and preferred contraception for the patient; should a
   woman become pregnant or suspect she is pregnant while she or her partner is
   participating in this study, she should inform her treating physician immediately; men
   treated or enrolled on this protocol must also agree to use adequate contraception
   before the study, for the duration of study participation, and 4 months after
   completion of MK-3475 (pembrolizumab) and interferon-gamma administration

   - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

   - Has disease that is suitable for local therapy administered with curative intent

   - Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks
   (6 weeks for nitrosoureas or mitomycin C) before entering the study

   - Patients who have had an allogeneic stem cell transplant are excluded

   - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2

   - Patients who have received an investigational agent or have used an investigational
   device within 4 weeks of the first dose of study drug

   - Has a history of a well-characterized and defined immune deficiency before the
   diagnosis of MF/SS or is receiving systemic steroid therapy greater than 10mg/day of
   prednisone or equivalent within 4 weeks or any other form of immunosuppressive therapy
   within 7 days before the first dose of trial treatment; the use of physiologic
   replacement doses of corticosteroids, along with topical, inhaled and local injection
   is discussed

   - Has had a prior monoclonal antibody within 4 weeks before study day 1 or who has not
   recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more
   than 4 weeks earlier

      - Note: the following will not be exclusionary: patients may have any grade
      alopecia or lymphopenia and still participate if other inclusion/exclusion
      criteria are met; patients may have grade 1 or 2 neuropathy at baseline and still
      participate if other inclusion/exclusion criteria are met

   - Has a known additional malignancy that is progressing or requires active treatment;
   exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
   skin that has undergone potentially curative therapy, or in situ cervical cancer

   - Patients with known brain metastases should be excluded from this clinical trial;
   patients with carcinomatous meningitis should also be excluded; patients with
   previously treated brain metastases may participate provided they are stable (without
   evidence of progression by imaging using the identical imaging modality for each
   assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan,
   for at least 4 weeks before the first dose of trial treatment and any neurologic
   symptoms have returned to baseline), have no evidence of new or enlarging brain
   metastases, and are not using steroids for at least 7 days before trial treatment

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MK-3475 (pembrolizumab) and interferon-gamma; patients who are
   hypersensitive to Escherichia (E). coli are also excluded

   - Has an active autoimmune disease that has required systemic treatment in the past 2
   years (i.e., with use of disease modifying agents, corticosteroids, or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment

   - Has a history of (non-infectious) pneumonitis that required steroids or current
   pneumonitis

   - Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the trial, interfere with the patient's
   participation for the full duration of the trial, or is not in the best interest of
   the patient to participate, in the opinion of the treating investigator

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, interstitial lung disease or active, non-infectious pneumonitis, congestive
   heart failure New York Heart Association (NYHA) grade >= 3, unstable angina pectoris,
   cardiac arrhythmia, or psychiatric illness/social situations that would limit
   compliance with study requirements

   - Pregnant women are excluded from this study; breastfeeding should be discontinued if
   the mother is treated with MK-3475 (pembrolizumab); patients are excluded from this
   study if pregnant or breastfeeding, or expecting to conceive or father children within
   the projected duration of the trial, starting with the screening visit through 120
   days after the last dose of trial treatment

   - Patients who are human immunodeficiency virus (HIV) positive may participate IF they
   meet the following eligibility requirements:

      - They must be stable on their anti-retroviral regimen, and they must be healthy
      from an HIV perspective

      - They must have a CD4 count of greater than 250 cells/mcL

      - They must not be receiving prophylactic therapy for an opportunistic infection

      - Must be on antiretroviral therapy and there must be minimal interactions or
      overlapping toxicity of the antiretroviral therapy with the experimental cancer
      treatment

      - HIV viral load must be < 200 copies/ mm^3 by standard clinical assays

   - Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected)

      - Note: the following will not be exclusionary:

         - A positive hepatitis B serology indicative of previous immunization (i.e.,
         HBsAb positive and hepatitis B virus core antibody [HBcAb] negative), or a
         fully resolved acute hepatitis B virus (HBV) infection

         - Patients with chronic HBV suppressed by appropriate antiretroviral therapy
         with activity against HBV, as outlined in Department of Health and Human
         Services (DHHS) guidelines

         - Positive HCV serology but no detectable HCV RNA, indicative of spontaneously
         cleared HCV infection

         - Patients who have been successfully treated for HCV as long as therapy for
         HCV has been completed

   - Has received a live vaccine within 30 days before to the first dose of trial
   treatment; examples of live vaccines include, but are not limited to, the following:
   measles, mumps, rubella, chicken pox, yellow fever, seasonal flu (some), H1N1 flu,
   rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine; seasonal flu vaccines that
   do not contain live virus are permitted

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the trial

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong
650-498-8604
Recruiting