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
A Phase II Trial of MK-3475 (Pembrolizumab) and Interferon Gamma 1-b Combination Immunotherapy in Patients With Previously Treated Mycosis Fungoides and Sezary Syndrome (Treatment Group 1) and in Patients With Advanced Synovial Sarcoma (Treatment Group 2)
4 other identifiers
interventional
28
1 country
7
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Dec 2017
Longer than P75 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 22, 2017
CompletedFirst Posted
Study publicly available on registry
February 24, 2017
CompletedStudy Start
First participant enrolled
December 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2021
CompletedResults Posted
Study results publicly available
August 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 14, 2023
CompletedOctober 25, 2023
October 1, 2023
3.3 years
February 22, 2017
June 10, 2022
October 3, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR)
Participants in Treatment Group 1 will be assessed for response and progression using standard response criteria in patients with Mycosis Fungoides and Sezary syndrome. Per Global Response Score determined by evaluating skin, lymph nodes, internal organs (viscera), and blood specimens: Complete Response (CR), complete disappearance of all clinical evidence of disease; Partial Response (PR), regression of measurable disease. Participants in Treatment Group 2 will be assessed for response and progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR) disappearance of all lesions and no new lesion; Partial Response (PR), 30% or greater reduction in tumor size and no new lesions. The ORR is defined as CR combined with PR. Will be assessed using binomial proportion. Best response at any timepoint was used to determine ORR.
Up to 2 years
Secondary Outcomes (6)
Incidence of Adverse Events
Up to 2 years and 1 months
Time to Response (TTR)
Time interval between the date of first treatment and the date of response (complete response [CR]/partial response [PR]), up to 2 years
Duration of Response (DOR)
Time interval between the date of first response (CR/PR) and the date of progression, up to 2 years and 11 months
Progression-free Survival (PFS)
Time from enrollment to disease progression or death, whichever occurs earlier, based upon investigator assessment, up to 3 years
Event-free Survival (EFS)
Termination due to toxicity, initiation of next significant treatment, progressive disease, or death of any cause, up to 2 years
- +1 more secondary outcomes
Other Outcomes (1)
Biomarkers in Tumor and Blood Assessed by Immunohistochemistry, Mass Spectrometry, Nanostring, Sequencing, and Enzyme-linked Immunosorbent Assay
Up to 3 years
Study Arms (2)
Group I (pembrolizumab, interferon gamma-1b)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles 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.
Group II (pembrolizumab, interferon gamma-1b)
EXPERIMENTALPatients pembrolizumab IV over 30 minutes on day 1 and interferon gamma-1b SC once a week. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unexpected toxicity.
Interventions
Given SC
Ancillary studies
Given IV
Eligibility Criteria
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
- +25 more criteria
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
- 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
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
FHCC South Lake Union
Seattle, Washington, 98109, United States
Related Publications (1)
Schroeder BA, Black RG, Spadinger S, Zhang S, Kohli K, Cao J, Mantilla JG, Conrad EU, Riddell SR, Jones RL, Yee C, Pollack SM. Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy. J Immunother Cancer. 2020 Apr;8(1):e000247. doi: 10.1136/jitc-2019-000247.
PMID: 32269142DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Anna Wright
- Organization
- Cancer Immunotherapy Trials Network
Study Officials
- PRINCIPAL INVESTIGATOR
Michael S Khodadoust, MD
Cancer Immunotherapy Trials Network
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 22, 2017
First Posted
February 24, 2017
Study Start
December 14, 2017
Primary Completion
April 8, 2021
Study Completion
March 14, 2023
Last Updated
October 25, 2023
Results First Posted
August 30, 2022
Record last verified: 2023-10