Hodgkin DiseasePhase 2CheckMate 744NCT02927769
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
A Phase 2 study testing Nivolumab, brentuximab vedotin and bendamustine in people with Hodgkin Disease, run by Bristol-Myers Squibb at 79 sites in 11 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 5 to 30 years
- Conditions the study is for
- Hodgkin Disease
- What is being tested?
- Nivolumab, brentuximab vedotin and bendamustine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 79 sitesin 11 countries
- Study dates
- 28 Mar 2017to 28 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
79 sites in 11 countries.
79 sites in 11 countries
United States43 sites
Children's Healthcare Of Atlanta
Atlanta, Georgia, 30322
Childrens Hospital of Colorado
Aurora, Colorado, 80045
Local Institution - 0042
Austin, Texas, 78723
Local Institution - 0070
Baltimore, Maryland, 21287
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Dana Farber Cancer Institute.
Boston, Massachusetts, 02215
Local Institution - 0068
Buffalo, New York, 14263
Local Institution
Chapel Hill, North Carolina, 27599
Carolinas Medical Center
Charlotte, North Carolina, 28203
Cincinnati Children'S Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Local Institution - 0089
Columbus, Ohio, 43205
Local Institution - 0071
Dallas, Texas, 75235
Local Institution - 0097
Detroit, Michigan, 48201
Local Institution - 0067
Hackensack, New Jersey, 07601
Local Institution - 0090
Hershey, Pennsylvania, 17033-0850
Baylor College Of Medicine
Houston, Texas, 77030
University Of Iowa
Iowa City, Iowa, 52242
Local Institution - 0049
Jackson, Mississippi, 39216
Local Institution - 0062
Jacksonville, Florida, 32207
Local Institution - 0085
Kansas City, Missouri, 64108
Nevada Cancer Research Foundation
Las Vegas, Nevada, 89135
Loma Linda University Cancer Center
Loma Linda, California, 92350
Valley Children's Hospital
Madera, California, 93636
Local Institution - 0065
Milwaukee, Wisconsin, 53226
Vanderbilt University
Nashville, Tennessee, 37232-6310
Local Institution - 0047
New Brunswick, New Jersey, 08903
Smilow Cancer Hospital At Yale New Haven Hospital
New Haven, Connecticut, 06520
Children'S Hosp-Kings Daughter
Norfolk, Virginia, 23507-1910
Children'S Hospital & Research Center At Oakland
Oakland, California, 94609
University Of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children'S Hospital Of Orange County
Orange, California, 92868
Lucile Packard Children'S Research Hospital/Stanford Univ
Palo Alto, California, 94304
Childrens Hospital Of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children'S Hospital
Phoenix, Arizona, 85016
Childrens Hospital Of Pittsburgh Of Upmc
Pittsburgh, Pennsylvania, 15224
Virginia Commonwealth University
Richmond, Virginia, 23219
Primary Children's Hospital
Salt Lake City, Utah, 84113
Local Institution - 0091
San Diego, California, 92109
Local Institution - 0048
Seattle, Washington, 98105
Washington University School Of Medicine
St Louis, Missouri, 63110
Local Institution - 0069
St. Petersburg, Florida, 33701
Children'S National Medical Center
Washington D.C., District of Columbia, 20010
Nemours / A. I. duPont Hospital for Children
Wilmington, Delaware, 19803
France9 sites
Local Institution - 0030
Lille, 59037
Local Institution - 0029
Lyon, 69008
Local Institution - 0032
Marseille, 13011
Local Institution - 0028
Nantes, 44093
Local Institution - 0031
Paris, 75012
Local Institution - 0026
Paris, 75019
Local Institution - 0033
Toulouse, 31059
Local Institution - 0034
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511
Local Institution - 0027
Villejuif, 94805
Italy6 sites
Local Institution - 0024
Aviano (PN), 33081
Local Institution - 0020
Bologna, 40138
Local Institution - 0021
Genova, 16147
Local Institution - 0019
Monza (mb), 20900
Local Institution - 0023
Naples, 80123
Local Institution - 0022
Roma, 00161
United Kingdom6 sites
Local Institution
Birmingham, B15 2TH
Local Institution
Glasgow, G51 4TF
Local Institution - 0035
Leeds, North Yorkshire, LS1 3EX
Local Institution
Leeds, Yorkshire, LS9 7TF
Local Institution - 0002
London, NW1 2BU
Local Institution - 0012
Manchester, M13 9WL
Germany4 sites
Local Institution - 0056
Berlin, 13353
Local Institution - 0055
Giessen, 35392
Local Institution - 0057
Hanover, 30625
Local Institution - 0102
München, 80337
Canada3 sites
Local Institution
Calgary, Alberta, T3B 6A8
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H4A 3J1
Local Institution - 0092
Toronto, Ontario, M5G 1X8
Netherlands2 sites
Local Institution - 0001
Rotterdam, 3015 CN
Local Institution - 0006
Utrecht, 3584 CS
Spain2 sites
Local Institution - 0082
Barcelona, 08950
Local Institution - 0084
Madrid, 28009
About this study
Official title: 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.
- Conditions
- Hodgkin Disease
- Being tested
- Nivolumab, brentuximab vedotin, bendamustine
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558, Opdivo
Specified Dose on Specified Days
brentuximab vedotinBiological
Specified Dose on Specified Days
bendamustineBiological
Specified Dose on Specified Days
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab + brentuximab vedotin | Experimental | Not described Receives: Biological: Nivolumab; Biological: brentuximab vedotin |
| brentuximab vedotin + bendamustine | Experimental | Not described Receives: Biological: brentuximab vedotin; Biological: bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Measured: 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)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2016 (estimated)
- Study start28 Mar 2017
- Primary completion28 May 2024
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hodgkin DiseaseStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02927769
- Sponsor's protocol ID
- CA209-744
- Other IDs
- 2016-002347-41, 2016
- Acronym
- CheckMate 744
- Status last verified
- Jan 2025
- First submitted
- 6 Oct 2016
- Last updated
- 10 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
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.
PubMed 39745739Harker-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.
PubMed 36564047
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02927769
- Acronym / sponsor ID
- CheckMate 744 / CA209-744
- Conditions
- Hodgkin Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Study start
- 28 Mar 2017 (actual)
- Primary completion
- 28 May 2024 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 7 Oct 2016 (estimated)
- Results
- Posted 10 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + brentuximab vedotin | Experimental | Biological: Nivolumab, Biological: brentuximab vedotin |
| brentuximab vedotin + bendamustine | Experimental | Biological: brentuximab vedotin, Biological: bendamustine |
Who may qualify
- Ages
- 5 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: BMS-936558, OpdivoSpecified Dose on Specified Days | Biological | Nivolumab + brentuximab vedotin |
| brentuximab vedotinSpecified Dose on Specified Days | Biological | Nivolumab + brentuximab vedotin, brentuximab vedotin + bendamustine |
| bendamustineSpecified Dose on Specified Days | Biological | brentuximab vedotin + bendamustine |
Primary outcome
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1
Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
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
Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1
Time frame: At 3 years post first dose of study therapy
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.
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
Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
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
14 secondary outcomes
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)
Time frame: 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)
Time frame: At 3 years post first dose of study therapy
Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At 3 years post first dose
Duration of Response (DOR) by Investigator
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39745739Daw 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.
- Derived from this study: PubMed 36564047Harker-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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
79 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, brentuximab vedotin and bendamustine in people with Hodgkin Disease, run by Bristol-Myers Squibb at 79 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 79 sites in United States, France, Italy, United Kingdom, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1 (time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02927769, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.