Clinical Trial: Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: MK-3475 in Combination With Standard RCHOP Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma

Brief Summary: This pilot clinical trial studies the side effects of pembrolizumab and combination chemotherapy in treating patients with previously untreated diffuse large B-cell lymphoma or grade 3b follicular lymphoma. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab together with combination chemotherapy may be with a better treatment for diffuse large B-cell lymphoma or follicular lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To measure the toxicity profile of pembrolizumab (MK-3475) when co-administered with full-course RCHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) in subjects with previously untreated diffuse large B-cell lymphoma (DLBCL).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes including response rate, event-free survival, and overall survival after MK-3475 + RCHOP induction for subjects with previously untreated DLBCL.

TERTIARY OBJECTIVES:

I. To measure baseline expression of proteins in the programmed death-1 (PD-1) family on tumor cells and coexisting immune infiltrates, using archival tissue when available.

II. To measure peripheral blood T cell subsets before and after treatment using flow cytometry, and to measure baseline vitamin D (25-hydroxy, total).

III. To explore relationships with these parameters and likelihood of response to therapy and outcomes.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and prednisone orally (PO) on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed up to 5 years.


Sponsor: University of Washington

Current Primary Outcome:

  • Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 90 days after completion of study treatment ]
  • Treatment-related mortality [ Time Frame: Up to 5 years ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Event-free survival [ Time Frame: Time from diagnosis until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause, assessed up to 5 years ]
    Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
  • Overall survival [ Time Frame: Date of diagnosis to death from any cause, assessed up to 5 years ]
    Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
  • Response rate measured by tumor imaging [ Time Frame: Up to 6 weeks after course 6 ]
    Tumor imaging at baseline and 4-6 weeks, +/-7 days, after 6 courses of induction therapy with MK-3475 + RCHOP to determine remission status. Response will be measured according to 2014 Criteria ("The Lugano Classification").


Original Secondary Outcome:

  • Event-free survival [ Time Frame: Time from diagnosis until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause, assessed up to 5 years ]
    Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
  • Overall survival [ Time Frame: Date of diagnosis to death from any cause, assessed up to 5 years ]
    Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.
  • Response rate measured by tumor imaging [ Time Frame: Up to 6 weeks after Cycle 6 ]
    Tumor imaging at baseline and 4-6 weeks, +/-7 days, after 6 cycles of induction therapy with MK-3475 + RCHOP to determine remission status. Response will be measured according to 2014 Criteria ("The Lugano Classification").


Information By: University of Washington

Dates:
Date Received: August 31, 2015
Date Started: November 2015
Date Completion:
Last Updated: November 21, 2016
Last Verified: November 2016