Testing the Combination of Two Experimental Drugs MK-3475 (Pembrolizumab) and Interferon-gamma for the Treatment of Mycosis Fungoides and Sézary Syndrome and Advanced Synovial Sarcoma

Completed · Phase 2

Conditions studied: Metastatic Myxoid Liposarcoma, Metastatic Round Cell Liposarcoma, Metastatic Synovial Sarcoma, Recurrent Mycosis Fungoides and Sezary Syndrome, Refractory Mycosis Fungoides and Sezary Syndrome, Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage III Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7, Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7, Unresectable Synovial Sarcoma

In brief

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.

Key facts

Study ID

NCT03063632

Run by

National Cancer Institute (NCI)

People needed

28

Starts

2017-12-14

Expected to finish

2023-03-14

Last updated by the study team

2023-10-25

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• MYCOSIS FUNGOIDES /SEZARY SYNDROME (TREATMENT GROUP I)
• Stage IB-IVB Mycosis Fungoides or Sezary syndrome, 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 corticosteroids greater 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
• Age >= 18 years
• 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 (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) (performed within 10 days of treatment initiation) OR
• Measured or calculated creatinine clearance >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN (performed within 10 days of treatment initiation)
• 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 (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 (performed within 10 days of treatment initiation)
• The effects of MK-3475 (pembrolizumab) and interferon-gamma on the developing human fetus are unknown; for this reason and because anti-PD-1 agents and interferons may be teratogenic, 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

You may not qualify if…

• MYCOSIS FUNGOIDES /SEZARY SYNDROME (TREATMENT GROUP I):
• 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 because such transplants disrupt the normal immune response to a very substantial degree; in addition, emerging data suggests exacerbation of lethal graft versus host disease (GVHD) may occur in such patients when treated post allotransplant with PD-1 blockade
• 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 mycosis fungoides or Sezary syndrome or is receiving systemic steroid therapy greater than 10 mg/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
• 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; 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 because MK-3475 (pembrolizumab) is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-3475 (pembrolizumab), breastfeeding should be discontinued if the mother is treated with MK-3475 (pembrolizumab); these potential risks may also apply to Interferon-gamma; MK-3475 (pembrolizumab) and Interferon-gamma may have adverse effects on a fetus in utero; furthermore, it is not known if MK-3475 (pembrolizumab) or Interferon-gamma have transient adverse effects on the composition of sperm; 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:

Where it is running

• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• University of Pennsylvania/Abramson Cancer Center — Philadelphia, Pennsylvania, United States
• FHCC South Lake Union — Seattle, Washington, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.