Clinical Trial: Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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 Summary:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response rate (ORR), defined as a confirmed partial response (PR) or CR using global assessment standard response criteria for MF and SS [ Time Frame: Up to 5 years ]

A generalized linear model for the objective response rate will use a binomial error distribution. The model will include as covariates all available baseline predictors of the missing outcomes.


Original Primary Outcome: Objective response rate (ORR), defined as a confirmed partial response (PR) or CR using global assessment standard response criteria for MF and SS [ Time Frame: Up to 5 years ]

An estimate of ORR will be provided at the final analysis along with a 90% repeated confidence interval for two-stage designs. Listings of tumor response for each subject based on standard response criteria in MF and SS will be provided.


Current Secondary Outcome:

  • DOR [ Time Frame: The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard MF and SS response criteria, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Incidence of adverse events graded using the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 90 days after last dose of trial treatment ]
    Adverse experiences will be summarized as counts and frequencies by toxicity grade. Summary statistics (median and range) for time to onset of first drug-related toxicity will be provided.
  • OS [ Time Frame: The time from randomization to death due to any cause, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • PFS [ Time Frame: The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.


Original Secondary Outcome:

  • Time to response (TTR) [ Time Frame: The time from allocation to the first CR or PR, assessed up to 5 years ]
    The non-parametric Kaplan-Meier method will be used to estimate the median and its 95% confidence interval.
  • Duration of response (DOR) [ Time Frame: The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard MF and SS response criteria, assessed up to 5 years ]
    The non-parametric Kaplan-Meier method will be used to estimate the median and its 95% confidence interval.
  • PFS [ Time Frame: The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
    The non-parametric Kaplan-Meier method will be used to estimate the median and its 95% confidence interval.
  • Event-free survival (EFS) [ Time Frame: The time from allocation until the earliest of the following: (1) initiation of any treatment other than topical steroids, (2) progressive disease, or (3) death, assessed up to 5 years ]
    The non-parametric Kaplan-Meier method will be used to estimate the median and its 95% confidence interval.
  • Overall survival [ Time Frame: The time from allocation until death, assessed up to 5 years ]
    The non-parametric Kaplan-Meier method will be used to estimate the median and its 95% confidence interval.
  • Incidence of adverse events (AEs) graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 90 days after last dose of trial treatment ]
    Adverse experiences will be summarized as counts and frequencies by toxicity grade. Summary statistics (median and range) for time to onset of first drug-related toxicity will be provided.
  • Incidence of immune-related events of clinical interest (ECIs) (irECIs) graded using CTCAE version 4.0 [ Time Frame: Up to 90 days after last dose of trial treatment ]
    irECIs that are designated as AEs of special interest will be summarized in separate tables from other AEs. Any AE of unknown etiology associated with lambrolizumab exposure will be evaluated to determine if it is possibly an ECI of a potentially immunologic etiology (irECI).


Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 16, 2014
Date Started: October 2014
Date Completion:
Last Updated: January 31, 2017
Last Verified: November 2016