Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors

NCT05039073 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00002348NCI-2021-01655WINSHIP5260-21P30CA138292
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent Classic Hodgkin Lymphoma; Refractory Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall 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).

  Up to 16 cycles (each cycle is 21 days)

Secondary Outcomes (5)

• Complete response rate (CRR)

  Up to 16 cycles (each cycle is 21 days)

• Progression-free survival (PFS)

  From time of study enrollment until first documentation of progressive disease or death from any cause, assessed up to 5 years

• Overall survival (OS)

  From time of study enrollment until death from any cause, assessed up to 5 years

• Incidence of adverse events

  Up to 5 years

• Incidence of symptomatic toxicity

  Up to 5 years

Study Arms (1)

Treatment (brentuximab vedotin, nivolumab)

EXPERIMENTAL

Patients receive brentuximab vedotin 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.

Drug: Brentuximab Vedotin; Procedure: Hematopoietic Cell Transplantation; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

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)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (brentuximab vedotin, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (brentuximab vedotin, nivolumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (brentuximab vedotin, nivolumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (brentuximab vedotin, nivolumab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed classical Hodgkin lymphoma
• Patients must be 12 years of age or older
• Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios:
• Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen.
• Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen.
• If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine \[BV-AVD\] + radiation therapy \[RT\] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen
• No prior autologous or allogeneic transplant
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 for patients \> 18 years old, or Lansky performance status of \>= 50 for patients ages 12-18 years
• Enrolling patients must have measurable disease defined as a tumor or nodal mass \> 1.5 cm in at least one dimension
• Resolution of all prior toxicities, including peripheral neuropathy, to a =\< grade 1
• Absolute neutrophil count (ANC) \>= 750, unless disease related (within 28 days of cycle 1 day 1)
• Platelets \>= 50,000, unless disease related (within 28 days of cycle 1 day 1)
• Creatinine =\< upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =\< 3 x ULN (within 28 days of cycle 1 day 1)
• Bilirubin =\< 2 mg/dL (within 28 days of cycle 1 day 1)

You may not qualify if:

• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for \>= 2 years or which will not limit survival to \< 2 years
• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =\< grade 1
• Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis
• Active central nervous system (CNS) involvement with lymphoma
• Patients with hepatitis B (positive hepatitis B virus surface antigen \[HBsAg\] or hepatitis B virus core antibody \[HBcAb\]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll
• No active infection, or other active illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Interventions

Brentuximab Vedotin; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; 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; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Kristie Blum, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 9, 2021
• Study Start: May 2, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)