Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Composite Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Pembrolizumab

Prednisone

Rituximab

Vincristine

Immunoglobulins

Cortisone

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

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.

Doxorubicin Hydrochloride

Laboratory Biomarker Analysis

Vincristine Sulfate

Stephen Smith

This pilot phase I 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.

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.

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

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

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.

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.

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.

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").

National Cancer Institute (NCI)

University of Washington

Patients will 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.

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Prednisone: Given PO

Rituximab: Given IV

Vincristine Sulfate: Given IV

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.

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Prednisone: Given PO

Rituximab: Given IV

Vincristine Sulfate: Given IV

Age, Categorical

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr. Stephen Smith

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

Spots Global Cancer Trial Database for stage i follicular lymphoma