This phase II trial studies the effect of brentuximab vedotin and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory) that have been previously treated with brentuximab vedotin or checkpoint inhibitors. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin and nivolumab in combination may be an effective treatment in patients with relapsed or refractory classic Hodgkin lymphoma previously treated with brentuximab vedotin or checkpoint inhibitors.
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) with brentuximab vedotin (brentuximab)/nivolumab used in combination in patients in patients previously treated with brentuximab in combination with standard chemotherapy for Hodgkin lymphoma (HL). II. To determine the ORR with brentuximab/nivolumab in combination in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. SECONDARY OBJECTIVES: I. To determine the complete response rate (CRR) and progression-free survival (PFS) with brentuximab/nivolumab in patients previously treated with brentuximab in combination with standard chemotherapy for HL. II. To determine the CRR and PFS with brentuximab/nivolumab in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. III. To evaluate safety of this regimen using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 (v 5.0). IV. To determine the tolerability of this regimen using patient-reported outcomes including Patient Reported Outcomes (PRO)-CTCAE or pediatric PRO-CTCAE, neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity \[FACT/GOG-NTX\]), and fatigue quality of life (QOL) by strata. V. To determine the number of patients who proceed to autologous or allogeneic hematopoietic stem cell transplantation (HSCT). VI. To determine the number of patients who successfully undergo stem cell collection among those planning to proceed to autologous HSCT. OUTLINE: 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 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant. After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Given IV
Undergo HSCT
Given IV
Ancillary studies
Ancillary studies
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGEmory Saint Joseph's Hospital
Atlanta, Georgia, United States
RECRUITINGOverall response rate (ORR)
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Assessed per Lugano 2014 Criteria at any time point while on study therapy. Will be analyzed independently for each cohort (A and B).
Time frame: Up to 16 cycles (each cycle is 21 days)
Complete response rate (CRR)
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Will be determined per Lugano 2014 criteria at any disease assessment time point while the patient is receiving study therapy.
Time frame: Up to 16 cycles (each cycle is 21 days)
Progression-free survival (PFS)
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year PFS will be calculated, with standard errors estimated using the Greenwood formula. Patients alive without disease progression will be censored at last follow-up date.
Time frame: From time of study enrollment until first documentation of progressive disease or death from any cause, assessed up to 5 years
Overall survival (OS)
Will be described using the Kaplan-Meier methodology. 95% confidence intervals for 1-year and 2-year OS will be calculated, with standard errors estimated using the Greenwood formula. Patients who have not died will be censored at last follow-up date.
Time frame: From time of study enrollment until death from any cause, assessed up to 5 years
Incidence of adverse events
According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
Time frame: Up to 5 years
Incidence of symptomatic toxicity
Evaluated by Patient Reported Outcomes (PRO)-CTCAE or Pediatric PRO-CTCAE.
Time frame: Up to 5 years
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