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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hodgkin Disease

Intervention / Treatment
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* Biological: Nivolumab
* Biological: brentuximab vedotin
* Biological: bendamustine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab + brentuximab vedotin<br> | Biological: Nivolumab<br>* Specified Dose on Specified Days<br>* Other names: Opdivo;Biological: brentuximab vedotin<br>* Specified Dose on Specified Days<br>|
| Experimental: brentuximab vedotin + bendamustine<br> | Biological: brentuximab vedotin<br>* Specified Dose on Specified Days<br>Biological: bendamustine<br>* Specified Dose on Specified Days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival (EFS) | Low Risk Group. Based on blinded independent central review (BICR) | Up to 5 years | 
| Complete Metabolic Response (CMR) rate prior to HDCT/ASCT | Standard Risk Group. This is the rate prior to high-dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) based on the blinded independent central review (BICR) using Lugano 2014 criteria. | Up to 5 years | 
| Complete Metabolic Response (CMR) rate at any time prior to radiation therapy | Low Risk Group. The CMR rate is defined as the proportion of all response-evaluable participants who, assessed by the BICR, achieve best response of CMR using Lugano 2014 criteria. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) after 4 cycles of nivolumab + brentuximab vedotin treatment | Based on blinded independent central review (BICR) | Up to 12 weeks | 
| Progression Free Survival Rate (PFSR) | Based on the blinded independent central review (BICR) | Up to 5 years | 
| Duration of Response (DOR) | Based on the blinded independent central review (BICR) | Up to 5 years | 
| Incidence of serious and non-serious adverse events of nivolumab (BMS-936558) and brentuximab when given in combination. | measured by number of patients | Up to 5 years | 
| Incidence of clinically significant abnormalities in general laboratory tests of nivolumab (BMS-936558) and brentuximab when given in combination. | Hematology, Chemistry and Urinalysis | Up to 5 years | 
| Incidence of clinically significant vital sign measurements of nivolumab (BMS-936558) and brentuximab when given in combination. | Temperature, Blood Pressure and Heart Rate | Up to 5 years | 
| Complete Metabolic Response (CMR) rate prior to HDCT/ASCT | Standard Risk Group. This is the rate prior to high-dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) based on investigator assessments using Lugano 2014 criteria. | Up to 5 years | 
| Complete Metabolic Response (CMR) rate at any time prior to radiation therapy | Low Risk Group. This is the rate prior to radiation therapy based on investigator assessments using Lugano 2014 criteria. | Up to 5 years | 
| Event Free Survival (EFS) | Low Risk Group. Based on investigator assessments | Up to 5 years | 
| Overall Response Rate (ORR) after 4 cycles of nivolumab + brentuximab vedotin treatment | Both Risk Groups. Based on investigator assessments | Up to 12 weeks | 
| Progression Free Survival Rate (PFSR) | Both Risk Groups. Based on investigator assessments | Up to 5 years | 
| Duration of Response (DOR) | Both Risk Groups. Based on investigator assessments | Up to 5 years |