Clinical Trials /

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

NCT03063632

Description:

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 (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor 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.

Related Conditions:
  • Mycosis Fungoides
  • Sezary Syndrome
  • Synovial Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome
  • Official Title: A Phase II Trial of Pembrolizumab and Interferon Gamma 1-b Combination Immunotherapy in Patients With Previously Treated MF/SS

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-00265
  • SECONDARY ID: NCI-2017-00265
  • SECONDARY ID: CITN-13
  • SECONDARY ID: CITN-13
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: U01CA154967
  • NCT ID: NCT03063632

Conditions

  • Recurrent Mycosis Fungoides and Sezary Syndrome
  • Refractory Mycosis Fungoides
  • Stage IB Mycosis Fungoides and Sezary Syndrome
  • Stage II Mycosis Fungoides and Sezary Syndrome
  • Stage IIA Mycosis Fungoides and Sezary Syndrome
  • Stage IIB Mycosis Fungoides and Sezary Syndrome
  • Stage III Mycosis Fungoides and Sezary Syndrome
  • Stage IIIA Mycosis Fungoides and Sezary Syndrome
  • Stage IIIB Mycosis Fungoides and Sezary Syndrome
  • Stage IV Mycosis Fungoides and Sezary Syndrome
  • Stage IVA Mycosis Fungoides and Sezary Syndrome
  • Stage IVB Mycosis Fungoides and Sezary Syndrome

Interventions

DrugSynonymsArms
Interferon Gamma-1bActimmune, N(Sup 2)-L-Methionyl-1-139-Interferon G, Recombinant Interferon Gamma-1bTreatment (pembrolizumab, interferon gamma-1b)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, interferon gamma-1b)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the overall response rate (ORR) of pembrolizumab (MK-3475) and interferon
      gamma-1b (IFN-G) (Actimmune) combination immunotherapy in subjects with previously treated
      mycosis fungoides (MF) or sezary syndrome (SS).

      SECONDARY OBJECTIVES:

      I. To explore the safety/tolerability and clinical activity of pembrolizumab (MK-3475) and
      IFN-G (Actimmune) in subjects with previously treated MF or SS with respect to safety and
      tolerability.

      II. To explore the safety/tolerability and clinical activity of pembrolizumab (MK-3475) and
      IFN-G (Actimmune) in subjects with previously treated MF or SS with respect to time to
      response (TTR).

      III. To explore the safety/tolerability and clinical activity of pembrolizumab (MK-3475) and
      IFN-G (Actimmune) in subjects with previously treated MF or SS with respect to duration of
      response (DOR).

      IV. To explore the safety/tolerability and clinical activity of pembrolizumab (MK-3475) and
      IFN-G (Actimmune) in subjects with previously treated MF or SS with respect to
      progression-free survival (PFS).

      V. To explore the safety/tolerability and clinical activity of pembrolizumab (MK-3475) and
      IFN-G (Actimmune) in subjects with previously treated MF or SS with respect to event-free
      survival (EFS).

      TERTIARY OBJECTIVES:

      I. To investigate the relationship between the following putative biomarkers for combination
      immunotherapy of pembrolizumab (MK-3475) and IFN-gamma (Actimmune) and clinical outcomes (as
      measured by safety/tolerability and ORR, DOR, PFS, EFS) in subjects with previously treated
      MF/SS, including tumor/microenvironment (PD-1/PD-L1/PD-L2 expression, cytotoxic T lymphocyte
      [CTL]s, regulatory T cell [Treg]s, macrophages, dendritic cell [DC]s; nanostring gene
      expression profile), systemic immune response (flow cytometry, mass cytometry [CyTOF],
      Luminex multiplexed cytokine profile), and molecular/genomic immune correlates (exome
      sequencing, high throughput sequencing [HTS] for T cell receptor [TCR]).

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat
      every 3 weeks for up to 2 years in the absence of disease progression or unexpected
      toxicity. Patients also receive interferon gamma-1b subcutaneously (SC) 3 times per week for
      12 weeks, and then follow 3 weeks on and 3 weeks off schedule for up to 2 years in the
      absence of disease progression or unexpected toxicity.

      After completion of study treatment, patients are follow up for 30 days and then every 12
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, interferon gamma-1b)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity. Patients also receive interferon gamma-1b SC 3 times per week for 12 weeks, and then follow 3 weeks on and 3 weeks off schedule for up to 2 years in the absence of disease progression or unexpected toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Stage IB-IVB MF/SS, and who have relapsed, are refractory, or progressed after at
                 least one standard systemic therapy
    
              -  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
    
                   -  >= 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 alemutuzumab for which the washout is at
                      least 8 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 therapeutic doses of systemic corticosteroids; patients who are
                      on physiologic doses of corticosteroids (prednisone equivalent 10mg/day or less)
                      may participate, however, they must be on a stable dose for at least 4 weeks
                      prior to 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 prior to 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
    
              -  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
    
              -  Absolute neutrophil count (ANC) >= 1500/mcL
    
              -  Platelets >= 100000/mcL
    
              -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
    
              -  Creatinine =< 1.5 x upper limit normal (ULN) OR
    
              -  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
    
              -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total
                 bilirubin levels > 1.5 x ULN
    
              -  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
    
              -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
                 patient is receiving anticoagulant therapy as long as PT or partial thromboplastin
                 time (PTT) is within therapeutic range of intended use of anticoagulants
    
              -  Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving
                 anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
                 use of anticoagulants
    
              -  Women of child-bearing potential and men must agree to use adequate contraception
                 (hormonal or barrier method of birth control; abstinence) prior 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 prior to 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 childbearing 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 prior to the study, for the duration of study participation, and 4
                 months after completion of 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 2 weeks
                 (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
    
              -  Patients who have had an allogeneic stem cell transplant are excluded unless they
                 have lost their donor graft subsequent to transplant, thus reducing the risk of graft
                 versus host disease (GVHD) associated with PD1 blockade
    
              -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
    
              -  Patients who are currently participating and receiving study therapy or have
                 participated in a study of an investigational agent and received study therapy or
                 used an investigational device within 4 weeks of the first dose of treatment
    
              -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
                 other form of immunosuppressive therapy within 7 days prior to 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 prior to 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 prior to 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 prior to trial treatment
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to 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; 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
    
              -  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 prior 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
    
              -  Has received prior therapy within 4 weeks with anti-CD137 or anti-cytotoxic
                 T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any
                 other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
                 pathways); has received prior alemtuzumab within 8 weeks
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall response rate per global assessment of MF and SS (confirmed and investigator assessed)
    Time Frame:Up to 1 year
    Safety Issue:
    Description:Binomial proportion.

    Secondary Outcome Measures

    Measure:Duration of response
    Time Frame:Time interval between the date of first response (complete response/partial response) and the date of progression, assessed up to 1 year
    Safety Issue:
    Description:Kaplan-Meier method.
    Measure:Event-free survival
    Time Frame:Termination due to toxicity, initiation of next significant treatment, progressive disease, or death of any cause, assessed up to 1 year
    Safety Issue:
    Description:Kaplan-Meier method.
    Measure:Incidence of study drug related sever adverse events assessed by the Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Progression-free survival
    Time Frame:Time from enrollment to disease progression or death, whichever occurs earlier, based upon investigator assessment, assessed up to 1 year
    Safety Issue:
    Description:Kaplan-Meier method.
    Measure:Time to response
    Time Frame:Up to 1 year
    Safety Issue:
    Description:Simple statistics.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:National Cancer Institute (NCI)

    Last Updated

    April 18, 2017