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 (CheckMate 744)

Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)

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.

Study Overview

• Status: Completed
• Conditions: Hodgkin Disease
• Intervention / Treatment: Biological: Nivolumab; Biological: brentuximab vedotin; Biological: bendamustine

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Local Institution
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Local Institution - 0092
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • The Montreal Children's Hospital of the MUHC
• Czechia
  • Praha 5, Czechia, 150 06
    • Klinika detske hematologie a onkologie
• France
  • Lille cedex, France, 59037
    • Local Institution - 0030
  • Lyon Cedex 08, France, 69008
    • Local Institution - 0029
  • Marseille, France, 13011
    • Local Institution - 0032
  • Nantes, France, 44093
    • Local Institution - 0028
  • Paris, France, 75019
    • Local Institution - 0026
  • Paris, France, 75012
    • Local Institution - 0031
  • Toulouse cedex 9, France, 31059
    • Local Institution - 0033
  • Villejuif, France, 94805
    • Local Institution - 0027
  • Meurthe-et-Moselle
    • Vandoeuvre lès Nancy, Meurthe-et-Moselle, France, 54511
      • Local Institution - 0034
• Germany
  • Berlin, Germany, 13353
    • Local Institution - 0056
  • Giessen, Germany, 35392
    • Local Institution - 0055
  • Hannover, Germany, 30625
    • Local Institution - 0057
  • Muenchen, Germany, 80337
    • Local Institution - 0102
• Ireland
  • Dublin, Ireland, Dublin 8
    • Local Institution - 0017
• Italy
  • Aviano (PN), Italy, 33081
    • Local Institution - 0024
  • Bologna, Italy, 40138
    • Local Institution - 0020
  • Genova, Italy, 16147
    • Local Institution - 0021
  • Monza (mb), Italy, 20900
    • Local Institution - 0019
  • Napoli, Italy, 80123
    • Local Institution - 0023
  • Roma, Italy, 00161
    • Local Institution - 0022
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • Local Institution - 0001
  • Utrecht, Netherlands, 3584 CS
    • Local Institution - 0006
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution
  • Krakow, Poland, 30-663
    • Local Institution
• Spain
  • Barcelona, Spain, 08950
    • Local Institution - 0082
  • Madrid, Spain, 28009
    • Local Institution - 0084
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Local Institution
  • Glasgow, United Kingdom, G51 4TF
    • Local Institution
  • London, United Kingdom, NW1 2BU
    • Local Institution - 0002
  • Manchester, United Kingdom, M13 9WL
    • Local Institution - 0012
  • North Yorkshire
    • Leeds, North Yorkshire, United Kingdom, LS1 3EX
      • Local Institution - 0035
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS9 7TF
      • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Loma Linda, California, United States, 92350
      • Loma Linda University Cancer Center
    • Madera, California, United States, 93636
      • Valley Children's Hospital
    • Oakland, California, United States, 94609
      • Children'S Hospital & Research Center At Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children'S Research Hospital/Stanford Univ
    • San Diego, California, United States, 92109
      • Local Institution - 0091
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Childrens Hospital of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Smilow Cancer Hospital At Yale New Haven Hospital
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours / A. I. duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Local Institution - 0062
    • Saint Petersburg, Florida, United States, 33701
      • Local Institution - 0069
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0070
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute.
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0097
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Local Institution - 0049
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Local Institution - 0085
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Research Foundation
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0067
    • New Brunswick, New Jersey, United States, 08903
      • Local Institution - 0047
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 0068
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Local Institution
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Local Institution - 0089
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Local Institution - 0090
    • Philadelphia, Pennsylvania, United States, 19104
      • Childrens Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Childrens Hospital Of Pittsburgh Of Upmc
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6310
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78723
      • Local Institution - 0042
    • Dallas, Texas, United States, 75235
      • Local Institution - 0071
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507-1910
      • Children'S Hosp-Kings Daughter
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98105
      • Local Institution - 0048
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Local Institution - 0065

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + brentuximab vedotin	Biological: Nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Biological: brentuximab vedotin; Specified Dose on Specified Days
Experimental: brentuximab vedotin + bendamustine	Biological: brentuximab vedotin; Specified Dose on Specified Days; Biological: bendamustine; Specified Dose on Specified Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)	Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved a best response of complete metabolic response (CMR) or partial metabolic response (PMR). 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 Partial metabolic response (PMR): Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline; New lesions: None; Bone marrow: Residual uptake higher than normal, reduced from baseline. Participants who came off early for toxicity without CMR or PMR were evaluable.	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)	Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by BICR or death. Progressive Disease (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. Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Based on Kaplan-Meier Estimates.	At 3 years post first dose of study therapy
Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)	Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, DOR was censored on the date of last tumor assessment. Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent therapy. 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 Partial metabolic response (PMR): Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline; New lesions: None; Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates	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	The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, 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 come off 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 Investigator - 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 Investigator - Cohort 2	The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, 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)
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator	Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieve a best response of complete metabolic response (CMR) or partial metabolic response (PMR). 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 Partial metabolic response: Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline; New lesions: None; Bone marrow: Residual uptake higher than normal, reduced from baseline Participants who came off early for toxicity without CMR or PMR were evaluable.	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 Investigator	Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by investigator or death. Progressive Disease (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. Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Based on Kaplan-Meier Estimates.	At 3 years post first dose
Duration of Response (DOR) by Investigator	Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment. Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. 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 Partial metabolic response: Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline; New lesions: None; Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates.	From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
The Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).
The Number of Participants With Serious Adverse Events (SAEs)	A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe); Requires inpatient hospitalization or causes prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event.	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
The Number of Participants With Abnormal Laboratory Values for Specific Thyroid Tests	The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests.	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
The Number of Participants With Abnormal Laboratory Values for Liver Tests	The Number of Participants with Abnormal Laboratory Values for Liver Tests.	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
Number of Participants With Abnormal Vital Signs Reported as Adverse Events	Temperature, blood pressure, and heart rate abnormalities reported as adverse events.	From first dose to 100 days after last dose of study therapy (assessed for an average of 7 months up until a maximum of 10 months).

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Seagen Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimated): October 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Immunoconjugates; Immunotoxins; Nivolumab; Bendamustine Hydrochloride; Brentuximab Vedotin
• Other Study ID Numbers: CA209-744; 2016-002347-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No