Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

NCT04561206 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 20147NCI-2020-05332P30CA033572
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

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.

Conditions

Relapsed Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at 24 months in patients who achieve complete metabolic response (CMR) after 4 cycles of treatment

  Estimated using Kaplan-Meier product limit method.

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, assessed at 24 months

Secondary Outcomes (5)

• Complete metabolic response (CMR) rate

  After 4 or 8 cycles (each cycle is 21 days)

• Overall response rate (ORR)

  After 4 or 8 cycles (each cycle is 21 days)

• 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)

• 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

Study Arms (1)

Treatment (brentuximab vedotin, nivolumab)

EXPERIMENTAL

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.

Drug: Brentuximab Vedotin; Biological: Nivolumab

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (brentuximab vedotin, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (brentuximab vedotin, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• Platelets \>= 50,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
• Hemoglobin \>= 8 g/dL (no transfusion allowed within 3 days prior to screening)

You may not qualify if:

• 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:
• Inhaled or topical steroids and
• Adrenal replacement doses \> 10 mg daily prednisone equivalents in the absence of active autoimmune disease
• History of progressive multifocal leukoencephalopathy (PML)
• Prior diagnosis of inherited or acquired immunodeficiency
• Active pneumonitis or interstitial lung disease

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

University of Chicago Cancer Research Center

Chicago, Illinois, 60637, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Hackensack University Medical Center/John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Interventions

Brentuximab Vedotin; Nivolumab

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Alex F Herrera

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alex Herrera, MD

CONTACT

626-359-8111; aherrera@coh.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 23, 2020
• Study Start: November 12, 2021
• Primary Completion (Estimated): October 2, 2026
• Study Completion (Estimated): October 2, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

US (5)