Nivolumab With DA-REPOCH Chemotherapy Regimen in Treating Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma

This phase II trial studies how well nivolumab works with the DA-REPOCH chemotherapy regimen in treating patients with aggressive B-cell non-Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as dose-adjusted rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (DA-REPOCH), 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 nivolumab with DA-REPOCH may work better in treating patients with aggressive B-cell non-Hodgkin lymphoma.

PRIMARY OBJECTIVES: I. To determine 2-year progression-free survival (PFS) of nivolumab in combination with DA-REPOCH with short course nivolumab maintenance. SECONDARY OBJECTIVES: I. To determine the objective response rate (ORR), complete response (CR) rate, and duration of response to nivolumab in combination with DA REPOCH with short course nivolumab maintenance. II. To establish that nivolumab in combination with DA-REPOCH with short course nivolumab maintenance is feasible at standard dosing. III. To establish the toxicity profile of nivolumab in combination with DA-REPOCH with short course nivolumab maintenance at standard dosing. EXPLORATORY OBJECTIVES: I. To correlate the presence of major histocompatibility complex (MHC) class I and II by immunohistochemistry (IHC) with PFS. II. To correlate tumor and microenvironment expression of PD-L1 and microenvironment expression of PD-1 with PFS. III. To correlate cell of origin, MYC and Bcl-2 expression, Epstein-Barr virus (EBV)-positivity, and Ki67 proliferation index with response to treatment. IV. To determine the effect of nivolumab in combination with DA-REPOCH on immune cell subsets in the peripheral blood over time. V. To correlate circulating tumor (ct) deoxyribonucleic acid (DNA) with disease response by positron emission tomography (PET) imaging. VI. To track clonal evolution and detect the emergence of treatment-resistance by ct-DNA monitoring. OUTLINE: Patients receive rituximab intravenously (IV) and nivolumab IV over 60 minutes on day 1. Patients also receive etoposide, vincristine sulfate and doxorubicin hydrochloride IV continuously over 96 hours, cyclophosphamide IV bolus, and prednisone orally (PO) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After course 6, patients receive nivolumab IV over 60 minutes on day 1 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 3 years, and then every 6 months for 5 years.