Nivolumab & Brentuximab Vedotin Consolidation After Autologous SCT in Patients With High-Risk Classical Hodgkin Lymphoma

PRIMARY OBJECTIVE: I. Assess the efficacy of nivolumab plus brentuximab vedotin consolidation after autologous stem cell transplantation (ASCT) in participants with relapsed/refractory Hodgkin lymphoma (HL), as assessed by 18-month progression-free survival (PFS). SECONDARY OBJECTIVES: I. Estimate the overall survival (OS), the cumulative incidence of relapse/progression, the cumulative incidence of non-relapse mortality (TRM) in participants with relapsed/ refractory HL who receive nivolumab plus brentuximab vedotin consolidation after ASCT. II. Estimate the overall response rate to nivolumab plus brentuximab vedotin therapy in participants with measurable disease after ASCT. III. Establish the safety and tolerability of nivolumab plus brentuximab vedotin when used as consolidation after ASCT in participants with relapsed/ refractory HL. EXPLORATORY OBJECTIVES: I. Evaluate the Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) definition of indeterminate response to guide the management of patients regarding treatment past progressive disease. II. Explore the impact of nivolumab plus brentuximab vedotin therapy on immune reconstitution after ASCT. III. Explore the prognostic impact of and temporal dynamics of minimal residual disease (MRD) in the peripheral blood as assessed by the next-generation sequencing-based ClonoSEQ platform. IV. Explore the prognostic impact of 9p24.1 abnormalities in tumor tissue assessed by fluorescence in situ hybridization (FISH) on outcomes after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy. V. Explore the relationship between immune cells and Hodgkin and Reed/Sternberg (HRS) in tumor samples by 6-color quantitative spatial image analysis using the Vectra system, and correlate with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy. VI. Explore whether genetic alterations (e.g. gene expression profiles or genetic mutations) in HL tumor samples are associated with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy. OUTLINE: Beginning 30-60 days post-ASCT, patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 100 days, at 3, 6, 12, and 18 months from start of treatment, and then biannually thereafter.