Recruiting
Phase 2

Brentuximab & Nivolumab

Sponsor:

Emory University

Code:

NCT05039073

Conditions

Recurrent Classic Hodgkin Lymphoma

Refractory Classic Hodgkin Lymphoma

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

Brentuximab Vedotin

Hematopoietic Cell Transplantation

Nivolumab

Quality-of-Life Assessment

Questionnaire Administration

Study Details

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

Study ID

NCT05039073

Start date

May 2, 2022

Status verified date

Aug, 2025

Completion date

Nov 30, 2027

Anticipated

Primary completion date

Nov 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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)
  • Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following criteria: No evidence of co-infection with hepatitis B or C; CD4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1.
  • Females of child-bearing potential (FCBP) must have a negative urine pregnancy test prior to starting therapy. If the test is positive, pregnancy must be ruled out
  • FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and 6 months after completion of brentuximab and/or nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

  • A female of childbearing potential (FCBP) is a post-menarcheal woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
  • Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer >= 2 weeks before the start of study therapy
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
  • Evidence of a personally signed informed consent by patients >= 18 year old (YO) or parent or legally authorized representative (LAR) for patients 12-17 YO indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. Patients 12-17 will also be required to give assent to the process per institutional guidelines

Exclusion Criteria:

  • 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

Study Design

Enrollment

46 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (brentuximab vedotin, nivolumab)

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.

Interventions

Brentuximab Vedotin

Given IV

Hematopoietic Cell Transplantation

Undergo HSCT

Nivolumab

Given IV

Quality-of-Life Assessment

Ancillary studies

Questionnaire Administration

Ancillary studies

Primary outcome measure

  • Overall response rate (ORR) [ Time Frame: Up to 16 cycles (each cycle is 21 days) ]

Central Contacts and Locations

Locations

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Kristie A. Blum

404-778-5933kablum@emory.edu

Blair Dykeman

blair.dykeman@emory.edu

Principal Investigator:

Kristie Blum

Emory Saint Joseph's Hospital

Recruiting

Atlanta, Georgia, United States, 30342

Contacts

Marcela Algave, CRN

678-843-7544marcela.rodrigues.algave@emory.edu

Principal Investigator:

Jason T Romancik, MD

More Information

Sponsor

Emory University

Last update posted

Aug 22, 2025

Last verified

Aug, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Emory University on 2025-08-22.