A Phase 2 Study of MK-3475 for the Treatment of Relapsed/Refractory Mycosis Fungoides/Sezary Syndrome

National Cancer Institute (NCI)8 sites in 1 country24 target enrollmentOctober 15, 2014

ConditionsRecurrent Mycosis Fungoides and Sezary Syndrome Refractory Mycosis Fungoides and Sezary Syndrome Stage IB 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 IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7 Stage IIIB 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

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Recurrent Mycosis Fungoides and Sezary Syndrome
Sponsor: National Cancer Institute (NCI)
Enrollment: 24
Locations: 8
Primary Endpoint: Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement or has not responded to at least one type of treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells.

Detailed Description

PRIMARY OBJECTIVES: I. To assess the response rate of MK-3475 (pembrolizumab) in subjects with relapsed/refractory mycosis fungoides/Sezary syndrome (MF/SS). SECONDARY OBJECTIVES: I. To explore the clinical activity of MK-3475 in subjects with relapsed/refractory MF and SS with respect to the following endpoints: duration of response (DOR); progression-free survival (PFS); overall survival (OS). OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving complete response \[CR\]) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 12 weeks.

Registry

clinicaltrials.gov

Start Date

October 15, 2014

End Date

April 1, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•This trial will include subjects with stage IB-IVB MF/SS (maximal stage since diagnosis will determine eligibility), and who have relapsed, are refractory, or progressed after at least one standard systemic therapy; 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 and adverse event (AE) recovery period from previous treatments without treatment between documentation of relapse/progression and enrollment of specifically:
•\>= 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 alemtuzumab for which the washout is at least 8 weeks
•\>= 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic T-lymphocyte-associated protein 4 (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 AEs due to procedures performed or therapeutic agents administered
•\>= 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement doses of oral corticosteroids are allowed, topical corticosteroids are allowed)
•\>= 2 weeks for phototherapy
•\>= 1 week for topical therapy (including retinoid, nitrogen mustard, or imiquimod)
•Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale

Exclusion Criteria

•Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
•Note: patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
•Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
•Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
•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
•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, or in situ cervical cancer that has undergone potentially curative therapy
•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 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

Outcomes

Primary Outcomes

Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome

Time Frame: Up to 3.2 years

A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.

Secondary Outcomes

Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0(Up to 4 years)
Duration of Response(The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks)
Time to Onset of First Drug-related Toxicity(Up to 4 years)
Overall Survival (OS)(The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks)
Progression Free Survival (PFS)(The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks)