Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma
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|ClinicalTrials.gov Identifier: NCT02541565|
Recruitment Status : Completed
First Posted : September 4, 2015
Results First Posted : September 23, 2020
Last Update Posted : October 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|Composite Lymphoma Grade 3b Follicular Lymphoma Stage I Diffuse Large B-Cell Lymphoma Stage I Follicular Lymphoma Stage II Diffuse Large B-Cell Lymphoma Stage II Follicular Lymphoma Stage III Diffuse Large B-Cell Lymphoma Stage III Follicular Lymphoma Stage IV Diffuse Large B-Cell Lymphoma Stage IV Follicular Lymphoma||Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate||Phase 1|
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).
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||MK-3475 in Combination With Standard RCHOP Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma|
|Actual Study Start Date :||November 24, 2015|
|Actual Primary Completion Date :||December 18, 2018|
|Actual Study Completion Date :||December 18, 2018|
Experimental: Treatment (pembrolizumab, combination chemotherapy)
Patients receive pembrolizumab IV over 30 minutes on day 1 and prednisone 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.
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Vincristine Sulfate
- Number of Participants With a Grade 3 or Higher 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 ]The Primary Outcome measures toxicity, with particular attention to Events of Clinical Interest when adding MK-3475 to standard RCHOP therapy. The sample size of 30 patients will permit the estimation of a 40% incidence of grade 3-5 clinically relevant toxicity.
- Treatment-related Mortality [ Time Frame: Up to 5 years ]
- 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").
- Changes in T-cell Subsets [ Time Frame: Baseline to up to 5 years ]Tissue-based assays for tumor and immune infiltrate will be conducted centrally when archival tissue is available. These analyses will seek to identify alterations in T-cell subsets for comparison with historical studies, and exploration of association with treatment outcomes achieved with study therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02541565
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Stephen Smith||Fred Hutch/University of Washington Cancer Consortium|