A Study of Nivolumab Plus Brentuximab Vedotin in Patients Between 5 and 30 Years Old, With Hodgkin's Lymphoma (cHL), Relapsed or Refractory From First Line Treatment

NCT02927769 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CA209-7442016-002347-41
• Study Type: interventional
• Target: 72
• Locations: 11 countries
• Sites: 79

Brief Summary

The purpose of this study is to determine whether nivolumab plus brentuximab vedotin (followed by brentuximab vedotin plus bendamustine in patient with suboptimal response) is safe and effective in treating patients with Hodgkin's lymphoma (cHL). Eligible patients are children, adolescents, and young adults relapsed or refractory to first line.

Conditions

Hodgkin Disease

Outcome Measures

Primary Outcomes (3)

• Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1

  The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): * Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method

  From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).

• Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1

  Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death . PD : Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease CMR: Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy. Based on Kaplan-Meier Estimates.

  At 3 years post first dose of study therapy

• Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2

  The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): * Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method

  From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)

Secondary Outcomes (14)

• Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)

  From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).

• Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)

  At 3 years post first dose of study therapy

• Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)

  From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)

• Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1

  From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).

• Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1

  At 3 years post first dose of study therapy

Study Arms (2)

Nivolumab + brentuximab vedotin

EXPERIMENTAL

Biological: Nivolumab; Biological: brentuximab vedotin

brentuximab vedotin + bendamustine

EXPERIMENTAL

Biological: brentuximab vedotin; Biological: bendamustine

Interventions

Nivolumab BIOLOGICAL

Specified Dose on Specified Days

Also known as: BMS-936558, Opdivo

Nivolumab + brentuximab vedotin

brentuximab vedotin BIOLOGICAL

Specified Dose on Specified Days

Nivolumab + brentuximab vedotin; brentuximab vedotin + bendamustine

bendamustine BIOLOGICAL

Specified Dose on Specified Days

brentuximab vedotin + bendamustine

Eligibility Criteria

• Age: 5 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Classic Hodgkin Lymphoma (cHL), relapsed or refractory
• Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants \> 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
• One prior anti-cancer therapy that did not work

You may not qualify if:

• Active, known, or suspected autoimmune disease or infection
• Active cerebral/meningeal disease related to the underlying malignancy
• More than one line of anti-cancer therapy or no treatment at all
• Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
• Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Seagen Inc.: collaborator

Study Sites (79)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children'S Hospital

Phoenix, Arizona, 85016, United States

Location

Loma Linda University Cancer Center

Loma Linda, California, 92350, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

Children'S Hospital & Research Center At Oakland

Oakland, California, 94609, United States

Location

Children'S Hospital Of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children'S Research Hospital/Stanford Univ

Palo Alto, California, 94304, United States

Location

Local Institution - 0091

San Diego, California, 92109, United States

Location

Childrens Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital At Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Nemours / A. I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children'S National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Local Institution - 0062

Jacksonville, Florida, 32207, United States

Location

Local Institution - 0069

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare Of Atlanta

Atlanta, Georgia, 30322, United States

Location

University Of Iowa

Iowa City, Iowa, 52242, United States

Location

Local Institution - 0070

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute.

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0097

Detroit, Michigan, 48201, United States

Location

Local Institution - 0049

Jackson, Mississippi, 39216, United States

Location

Local Institution - 0085

Kansas City, Missouri, 64108, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Nevada Cancer Research Foundation

Las Vegas, Nevada, 89135, United States

Location

Local Institution - 0067

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0047

New Brunswick, New Jersey, 08903, United States

Location

Local Institution - 0068

Buffalo, New York, 14263, United States

Location

Local Institution

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Children'S Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Local Institution - 0089

Columbus, Ohio, 43205, United States

Location

University Of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Local Institution - 0090

Hershey, Pennsylvania, 17033-0850, United States

Location

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Childrens Hospital Of Pittsburgh Of Upmc

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232-6310, United States

Location

Local Institution - 0042

Austin, Texas, 78723, United States

Location

Local Institution - 0071

Dallas, Texas, 75235, United States

Location

Baylor College Of Medicine

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Children'S Hosp-Kings Daughter

Norfolk, Virginia, 23507-1910, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Local Institution - 0048

Seattle, Washington, 98105, United States

Location

Local Institution - 0065

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution

Calgary, Alberta, T3B 6A8, Canada

Location

Local Institution - 0092

Toronto, Ontario, M5G 1X8, Canada

Location

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H4A 3J1, Canada

Location

Klinika detske hematologie a onkologie

Prague, 150 06, Czechia

Location

Local Institution - 0034

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

Local Institution - 0030

Lille, 59037, France

Location

Local Institution - 0029

Lyon, 69008, France

Location

Local Institution - 0032

Marseille, 13011, France

Location

Local Institution - 0028

Nantes, 44093, France

Location

Local Institution - 0031

Paris, 75012, France

Location

Local Institution - 0026

Paris, 75019, France

Location

Local Institution - 0033

Toulouse, 31059, France

Location

Local Institution - 0027

Villejuif, 94805, France

Location

Local Institution - 0056

Berlin, 13353, Germany

Location

Local Institution - 0055

Giessen, 35392, Germany

Location

Local Institution - 0057

Hanover, 30625, Germany

Location

Local Institution - 0102

München, 80337, Germany

Location

Local Institution - 0017

Dublin, Dublin 8, Ireland

Location

Local Institution - 0024

Aviano (PN), 33081, Italy

Location

Local Institution - 0020

Bologna, 40138, Italy

Location

Local Institution - 0021

Genova, 16147, Italy

Location

Local Institution - 0019

Monza (mb), 20900, Italy

Location

Local Institution - 0023

Napoli, 80123, Italy

Location

Local Institution - 0022

Roma, 00161, Italy

Location

Local Institution - 0001

Rotterdam, 3015 CN, Netherlands

Location

Local Institution - 0006

Utrecht, 3584 CS, Netherlands

Location

Local Institution

Gdansk, 80-952, Poland

Location

Local Institution

Krakow, 30-663, Poland

Location

Local Institution - 0082

Barcelona, 08950, Spain

Location

Local Institution - 0084

Madrid, 28009, Spain

Location

Local Institution - 0035

Leeds, North Yorkshire, LS1 3EX, United Kingdom

Location

Local Institution

Leeds, Yorkshire, LS9 7TF, United Kingdom

Location

Local Institution

Birmingham, B15 2TH, United Kingdom

Location

Local Institution

Glasgow, G51 4TF, United Kingdom

Location

Local Institution - 0002

London, NW1 2BU, United Kingdom

Location

Local Institution - 0012

Manchester, M13 9WL, United Kingdom

Location

Related Publications (2)

• Daw S, Cole PD, Hoppe BS, Hodgson D, Beishuizen A, Garnier N, Buffardi S, Mascarin M, Lissat A, Mauz-Korholz C, Krajewski J, Akyol A, Crowe R, Anderson B, Xu Y, Drachtman RA, Kelly KM, Leblanc T, Harker-Murray P. Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial. JAMA Oncol. 2025 Mar 1;11(3):249-257. doi: 10.1001/jamaoncol.2024.5627.

  PMID: 39745739 DERIVED

• Harker-Murray P, Mauz-Korholz C, Leblanc T, Mascarin M, Michel G, Cooper S, Beishuizen A, Leger KJ, Amoroso L, Buffardi S, Rigaud C, Hoppe BS, Lisano J, Francis S, Sacchi M, Cole PD, Drachtman RA, Kelly KM, Daw S. Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults. Blood. 2023 Apr 27;141(17):2075-2084. doi: 10.1182/blood.2022017118.

  PMID: 36564047 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Nivolumab; Brentuximab Vedotin; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Oligopeptides; Peptides; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 7, 2016
• Study Start: March 28, 2017
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-01

Locations

PL (2); GB (6); DE (4); US (43); CZ (1); IE (1); CA (3); ES (2); IT (6); FR (9); NL (2)