A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab Without Stem Cell Consolidation in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Brentuximab Vedotin
- Conditions
- Relapsed Classic Hodgkin Lymphoma
- Sponsor
- City of Hope Medical Center
- Enrollment
- 31
- Locations
- 5
- Primary Endpoint
- Progression-free survival (PFS) at 24 months in patients who achieve complete metabolic response (CMR) after 4 cycles of treatment
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This phase II trial investigates how well brentuximab vedotin and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back after initial treatment (relapsed) or has not responded to initial treatment (refractory). 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. Nivolumab is an antibody that enhances the immune system to better fight Hodgkin lymphoma cells. Giving brentuximab vedotin and nivolumab may be able to defer stem cell transplant treatment and spare the considerable cost and toxicity on transplantation.
Detailed Description
PRIMARY OBJECTIVE: I. Assess the durability of response to brentuximab vedotin (BV) plus nivolumab (nivo) by 24-month progression-free survival (PFS) in participants (with relapsed/refractory classical Hodgkin lymphoma (RcHL) after frontline therapy) who achieved early complete metabolic response (CMR) (CMR after 4 cycles). SECONDARY OBJECTIVES: I. Estimate CMR and overall response rate (ORR) after 4 cycles and at the end of BV-nivo therapy. II. Estimate the PFS and overall survival (OS) for the entire cohort and for subgroups of patients defined by their response. III. Estimate the PFS and OS separately for responders who did and did not receive radiotherapy. IV. Evaluate the toxicities of BV-nivo in the study population. EXPLORATORY OBJECTIVES: I. Estimate the second PFS after salvage therapy for patients who progress after study therapy, and for the subset of these patients who proceeded to autologous stem cell transplant (ASCT). II. Explore the association between clinical outcomes and pathological tumor characteristics. III. Explore the association between clinical outcomes and circulating tumor deoxyribonucleic acid (ctDNA) characteristics (mutation profile, kinetics of clearance). OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and 6, 12, 18, 24, 36, 48, and 60 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented informed consent of the participant and/or legally authorized representative
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Be willing to provide tissue (either from a fresh core or excisional biopsy performed as standard of care, or from archival tissue) of a biopsy that was performed after frontline systemic therapy, and prior to starting protocol therapy
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Eastern Cooperative Oncology Group (ECOG) =\< 2
- •Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
- •Relapsed or refractory disease after no more than 1 line of prior therapy (not counting radiotherapy). However, a maximum of 5 patients with primary refractory disease may be enrolled in this study.
- •Note: Patients who received BV or an anti-PD-1/PD-L1 agent as part of frontline therapy are eligible if they achieved a CMR with frontline therapy and have not relapsed within 6 months from the end of frontline therapy Relapse must have been confirmed histologically (with hematopathology review at the participating institution)
- •Not a candidate for ASCT, based on age, co-morbidities, or patient preference. The reason for ASCT non-candidacy must be documented in the Case Report Form and verified by the site PI
- •Measurable disease (at least one non-bony fludeoxyglucose F-18 \[FDG\]-avid lesion \>= 1.5 cm in long axis)
Exclusion Criteria
- •Concomitant investigational therapy
- •Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette-Guerin \[BCG\], oral polio vaccine, and oral typhoid)
- •Grade \>= 2 peripheral neuropathy
- •History of prior \>= grade 3 hypersensitivity to either brentuximab vedotin or nivolumab
- •Known active central nervous system (CNS) involvement by lymphoma, including parenchymal and/or lymphomatous meningitis
- •History of another primary malignancy that has not been in remission for at least 3 years, with the following exceptions:
- •Non-melanoma skin cancer treated with curative intent
- •In situ cervical cancer
- •If the malignancy is expected to not require any treatment for at least 2 years (this exception should be discussed with the study PI)
- •Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Exceptions are:
Arms & Interventions
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Brentuximab Vedotin
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Progression-free survival (PFS) at 24 months in patients who achieve complete metabolic response (CMR) after 4 cycles of treatment
Time Frame: From start of protocol treatment to time of disease relapse/progression or death due to any cause, assessed at 24 months
Estimated using Kaplan-Meier product limit method.
Secondary Outcomes
- Overall response rate (ORR)(After 4 or 8 cycles (each cycle is 21 days))
- Complete metabolic response (CMR) rate(After 4 or 8 cycles (each cycle is 21 days))
- PFS(From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 5 years(each cycle is 21 days))
- Incidence of adverse events(Up to 30 days post-treatment)
- Overall survival (OS)(From start of protocol treatment to time of death due to any cause, assessed up to 5 years (each cycle is 21 days))