This phase II trial studies how well nivolumab and brentuximab vedotin work after stem cell transplant in treating patients with high-risk classical Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and brentuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
City of Hope Medical Center
Duarte, California, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
M D Anderson Cancer Center
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Progression-free Survival at 18 Months
Progression-free survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. When there is no censoring in progression-free survival prior to 18 months after the first dose of study treatment, the observed 18-month progression-free survival will be compared to the baseline of 65% by one-sided exact test of binomial proportion. In case of censoring in progression-free survival prior to 18 months after the first dose of study treatment, the Kaplan-Meier estimate for 18-month progression-free survival along with the Greenwood standard error estimator will be used for the testing of null hypothesis at 65%. Hodgkin Lymphoma(HL) response/progression was evaluated using 2014 Lugano Classification \[Cheson, Journal of Clinical Oncology 2014 Sep 20;32(27):3059-68\].
Time frame: From the first dose of study treatment to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed at 18 months.
Overall Survival at 18 Months
Overall survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
Time frame: From the first dose of study treatment to death from any cause, assessed up to 18 months
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