Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma

NCT02758717 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: RU051505INCI-2016-00468P30CA015083
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 9

Brief Summary

This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. 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. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Conditions

Ann Arbor Stage IB Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage III Hodgkin Lymphoma; Ann Arbor Stage IIIA Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Metabolic Response Rate

  The primary endpoint of this trial is the rate (percentage) of overall metabolic response. A metabolic response is defined as a participant who has achieved an objective status of Partial metabolic response (PMR) or Complete metabolic response (CMR) at the end of cycle 8. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMR: Score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size CMR: Score 1 (no uptake above background), 2 (uptake\<=mediastinum), or 3 (uptake \> mediastinum but \<= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst.

  Up to 8 cycles of treatment (approximately 29 weeks)

Secondary Outcomes (5)

• Number of Participants With an Overall Response of Complete Metabolic Response

  Up to end of course 8

• Duration of Response (DOR)

  30 months

• Progression-free Survival

  30 months

• Overall Survival

  30 months

• Number of Participants Experiencing at Least One Adverse Events Graded 3 or Higher Deemed at Least Possibly Related to Treatment

  Up to 8 cycles of treatment (approximately 29 weeks)

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 7 cycles and 6-8 weeks in cycle 8 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

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

You may qualify if:

• Classical Hodgkin lymphoma determined by local hematopathology review
• One of the following:
• Age \>= 60 years
• Age \< 60 years but unsuitable for standard chemotherapy because of a cardiac ejection fraction of \< 50%, a pulmonary diffusion capacity \< 80%, or a creatinine clearance \>= 30 and \< 60 mL/min, or refused standard chemotherapy despite efforts to convince them otherwise
• Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative
• Previously untreated with either chemotherapy, radiation therapy or either brentuximab vedotin or nivolumab, or another check point inhibitor
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Absolute neutrophil count (ANC) \>= 1500/mm\^3, unless secondary to bone marrow involvement; obtained =\< 7 days prior to registration
• Leukocytes \>= 3,000/mm\^3, obtained =\< 7 days prior to registration
• Platelet count \>= 100,000/mm\^3, obtained =\< 7 days prior to registration
• Hemoglobin \> 9.0 g/dL - unless determined by treating physician to be disease related, obtained =\< 7 days prior to registration
• Total bilirubin =\< 1.5 x upper limit of normal (ULN), obtained =\< 7 days prior to registration
• Aspartate aminotransferase (aspartate transaminase \[AST\]) =\< 2.5 x ULN, obtained =\< 7 days prior to registration
• Alanine aminotransferase (alanine transaminase \[ALT\]) =\< 2.5 x ULN, obtained =\< 7 days prior to registration
• Creatinine =\< 2.0 mg/dL, obtained =\< 7 days prior to registration

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Active, known or suspected autoimmune disease; note: subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Use of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications =\< 14 days of registration; Note: Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, patients with a prior history of known or suspected autoimmune disease, active hepatitis B virus surface antigen (HBV sAg+), active hepatitis C (if antibody \[Ab\]+ then polymerase chain reaction \[PCR\]+) indicating acute or chronic infection, and/or history of interstitial lung disease
• Allergy to brentuximab vedotin and/or nivolumab
• Uncontrolled intercurrent 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
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma
• Have received either of the study drugs
• \< 60 years who are considered candidates for standard chemotherapy
• \>= grade 2 peripheral neuropathy

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Cheson BD, Bartlett NL, LaPlant B, Lee HJ, Advani RJ, Christian B, Diefenbach CS, Feldman TA, Ansell SM. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020 Nov;7(11):e808-e815. doi: 10.1016/S2352-3026(20)30275-1. Epub 2020 Oct 1.

  PMID: 33010817 DERIVED

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

Results Point of Contact

• Title: Bruce D. Cheson, M.D.
• Organization: Lombardi Comprehensive Cancer Center

bdc4@georgetown.edu

507-266-0800

Study Officials

• Bruce D Cheson

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: April 12, 2016
• First Posted: May 2, 2016
• Study Start: May 13, 2016
• Primary Completion: August 13, 2019
• Study Completion: September 13, 2025
• Last Updated: September 9, 2025
• Results First Posted: September 22, 2020

Record last verified: 2025-08

Locations

US (9)