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

Phase 2

Completed

Conditions: Hodgkin Disease

Interventions: Biological: Nivolumab
Biological: brentuximab vedotin
Biological: bendamustine

Registration Number: NCT02927769

Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nivolumab + brentuximab vedotin	brentuximab vedotin	-
brentuximab vedotin + bendamustine	brentuximab vedotin	-
Nivolumab + brentuximab vedotin	Nivolumab	-
brentuximab vedotin + bendamustine	bendamustine	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With Serious Adverse Events (SAEs)	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)	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.
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)	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
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).	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
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).	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.
Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)	At 3 years post first dose of study therapy	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.
Progression Free Survival (PFS) Rate at 3 Years by Investigator	At 3 years post first dose	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.
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 Specific Thyroid 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)	The Number of Participants with Abnormal Laboratory Values for Liver Tests.
Number of Participants With Abnormal Vital Signs 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).	Temperature, blood pressure, and heart rate abnormalities reported as adverse events.
Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1	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 Investigator - Cohort 2	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 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.
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator	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).	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.
Duration of Response (DOR) by Investigator	From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)	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.
The Number of Participants With Adverse Events (AEs)	From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).	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.

Trial Locations

Locations (73): Loma Linda University Cancer Center
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Loma Linda, California, United States
Children'S Hospital & Research Center At Oakland
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Oakland, California, United States
Children'S Hospital Of Orange County
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Orange, California, United States
Children'S National Medical Center
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Washington, District of Columbia, United States
Local Institution - 0062
🇺🇸
Jacksonville, Florida, United States
Local Institution - 0069
🇺🇸
Saint Petersburg, Florida, United States
Children's Healthcare Of Atlanta
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Atlanta, Georgia, United States
University Of Iowa
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Iowa City, Iowa, United States
Local Institution - 0049
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Jackson, Mississippi, United States
Washington University School Of Medicine
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Saint Louis, Missouri, United States
Local Institution - 0068
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Buffalo, New York, United States
Local Institution
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Glasgow, United Kingdom
Carolinas Medical Center
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Charlotte, North Carolina, United States
Local Institution - 0090
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Hershey, Pennsylvania, United States
Childrens Hospital Of Pittsburgh Of Upmc
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Pittsburgh, Pennsylvania, United States
Local Institution - 0071
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Dallas, Texas, United States
Children'S Hosp-Kings Daughter
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Norfolk, Virginia, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Local Institution - 0092
🇨🇦
Toronto, Ontario, Canada
Klinika detske hematologie a onkologie
🇨🇿
Praha 5, Czechia
Local Institution - 0034
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Vandoeuvre lès Nancy, Meurthe-et-Moselle, France
Local Institution - 0030
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Lille cedex, France
Local Institution - 0032
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Marseille, France
Local Institution - 0029
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Lyon Cedex 08, France
Local Institution - 0028
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Nantes, France
Local Institution - 0031
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Paris, France
Local Institution - 0033
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Toulouse cedex 9, France
Local Institution - 0027
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Villejuif, France
Local Institution - 0056
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Berlin, Germany
Local Institution - 0055
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Giessen, Germany
Local Institution - 0057
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Hannover, Germany
Local Institution - 0102
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Muenchen, Germany
Local Institution - 0017
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Dublin, Ireland
Local Institution - 0021
🇮🇹
Genova, Italy
Local Institution - 0023
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Napoli, Italy
Local Institution - 0001
🇳🇱
Rotterdam, Netherlands
Local Institution - 0022
🇮🇹
Roma, Italy
Valley Children's Hospital
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Madera, California, United States
Local Institution - 0006
🇳🇱
Utrecht, Netherlands
Local Institution - 0082
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Barcelona, Spain
Local Institution - 0084
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Madrid, Spain
Local Institution - 0002
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London, United Kingdom
Local Institution - 0012
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Manchester, United Kingdom
Local Institution - 0089
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Columbus, Ohio, United States
Local Institution - 0070
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Baltimore, Maryland, United States
Local Institution - 0091
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San Diego, California, United States
Dana Farber Cancer Institute.
🇺🇸
Boston, Massachusetts, United States
Nevada Cancer Research Foundation
🇺🇸
Las Vegas, Nevada, United States
Cincinnati Children'S Hospital Medical Center
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Cincinnati, Ohio, United States
Primary Children's Hospital
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Salt Lake City, Utah, United States
Local Institution - 0048
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Seattle, Washington, United States
Local Institution - 0035
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Leeds, North Yorkshire, United Kingdom
Childrens Hospital Of Philadelphia
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Philadelphia, Pennsylvania, United States
Local Institution - 0047
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New Brunswick, New Jersey, United States
Local Institution - 0067
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Hackensack, New Jersey, United States
Phoenix Children'S Hospital
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Phoenix, Arizona, United States
Local Institution - 0097
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Detroit, Michigan, United States
University Of Oklahoma Health Sciences Center
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Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
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Birmingham, Alabama, United States
Local Institution - 0065
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Milwaukee, Wisconsin, United States
Childrens Hospital of Colorado
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Aurora, Colorado, United States
Lucile Packard Children'S Research Hospital/Stanford Univ
🇺🇸
Palo Alto, California, United States
Nemours / A. I. duPont Hospital for Children
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Wilmington, Delaware, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Local Institution - 0026
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Paris, France
Local Institution - 0024
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Aviano (PN), Italy
Local Institution - 0020
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Bologna, Italy
Local Institution - 0019
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Monza (mb), Italy
Baylor College Of Medicine
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Houston, Texas, United States
Smilow Cancer Hospital At Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Local Institution - 0085
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Kansas City, Missouri, United States
Local Institution - 0042
🇺🇸
Austin, Texas, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States