Pembrolizumab in Combination With Chemotherapy for the Treatment of Frail Hodgkin Lymphoma Patients Ineligible for Standard Treatment

This phase II trial tests how well pembrolizumab in addition to chemotherapy (gemcitabine, brentuximab vedotin, and dacarbazine) works in treating frail patients with newly diagnosed Hodgkin lymphoma who aren't candidates for standard anthracycline-based treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. Dacarbazine is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells and slow down or stop cancer growth. Pembrolizumab in combination chemotherapy may be a safe and effective alternative treatment option for frail patients with Hodgkin lymphoma who can't receive standard anthracycline-based treatment.

PRIMARY OBJECTIVE: I. Estimate the best complete metabolic response (CMR) rate for frail patients with classical Hodgkin lymphoma (cHL) who receive pembrolizumab and gemcitabine (P-G). SECONDARY OBJECTIVES: I. Estimate CMR rate, overall response rate (ORR), progression-free-survival (PFS), duration of response (DOR), and overall response (OS) among patients who receive P-G (± pembrolizumab maintenance). II. Estimate CMR, overall response, PFS, DOR, and OS among patients who receive pembrolizumab, brentuximab vedotin, and dacarbazine (P-BV-D). III. Evaluate the toxicity of P-G, pembrolizumab maintenance, and P-BV-D. EXPLORATORY OBJECTIVES: I. Explore association between geriatric assessment measures (Cancer and Aging Research Group \[CARG\] geriatric assessment) and toxicity and efficacy in the elderly patients enrolled on this trial. II. Assess functional trajectory determined by short physical performance battery (SPPB) change score in the elderly patients enrolled on this trial. III. Explore the association between clinical outcomes and pathological tumor characteristics. OUTLINE: CYCLES 1-8: Patients receive pembrolizumab intravenously (IV) over 30 minutes and gemcitabine IV on day 1 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients without progressive disease during or at the completion of 8 cycles of P-G proceed to maintenance therapy. Patients with progressive disease during or at the completion of 8 cycles of P-G proceed to salvage therapy. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles (cycles 9-12) in the absence of disease progression or unacceptable toxicity. SALVAGE THERAPY: Patients receive pembrolizumab IV over 30 minutes, brentuximab vedotin IV over 30 minutes, and dacarbazine IV on day 1 of each cycle. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial and may undergo echocardiography (ECHO) at screening if indicated. After completion of study treatment, patients are followed up at 30 days and at 12, 18 (salvage patients), and 24 months.