Clinical trial NCT02927769: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2016-10-07
Enrollment: 72
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1
timeFrame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
measure: Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1
timeFrame: At 3 years post first dose of study therapy
measure: 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
timeFrame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
Secondary outcomes:
measure: Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)
timeFrame: 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).
measure: Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)
timeFrame: At 3 years post first dose of study therapy
measure: Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
timeFrame: From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
measure: Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1
timeFrame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
measure: Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1
timeFrame: At 3 years post first dose of study therapy
measure: 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
timeFrame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
measure: Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator
timeFrame: 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).
measure: Progression Free Survival (PFS) Rate at 3 Years by Investigator
timeFrame: At 3 years post first dose
measure: Duration of Response (DOR) by Investigator
timeFrame: From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
measure: The Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).
measure: The Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
measure: The Number of Participants With Abnormal Laboratory Values for Specific Thyroid Tests
timeFrame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
measure: The Number of Participants With Abnormal Laboratory Values for Liver Tests
timeFrame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
measure: Number of Participants With Abnormal Vital Signs Reported as Adverse Events
timeFrame: 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).
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children'S Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: Children'S Hospital & Research Center At Oakland
state: California
city: Orange
country: United States
facility: Children'S Hospital Of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children'S Research Hospital/Stanford Univ
state: California
city: San Diego
country: United States
facility: Local Institution - 0091
state: California
city: Aurora
country: United States
facility: Childrens Hospital of Colorado
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital At Yale New Haven Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours / A. I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children'S National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Local Institution - 0062
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 0069
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare Of Atlanta
state: Georgia
city: Iowa City
country: United States
facility: University Of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Local Institution - 0070
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute.
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - 0097
state: Michigan
city: Jackson
country: United States
facility: Local Institution - 0049
state: Mississippi
city: Kansas City
country: United States
facility: Local Institution - 0085
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Hackensack
country: United States
facility: Local Institution - 0067
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution - 0047
state: New Jersey
city: Buffalo
country: United States
facility: Local Institution - 0068
state: New York
city: Chapel Hill
country: United States
facility: Local Institution
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0089
state: Ohio
city: Oklahoma City
country: United States
facility: University Of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Local Institution - 0090
state: Pennsylvania
city: Philadelphia
country: United States
facility: Childrens Hospital Of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Childrens Hospital Of Pittsburgh Of Upmc
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Local Institution - 0042
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0071
state: Texas
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Norfolk
country: United States
facility: Children'S Hosp-Kings Daughter
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 0048
state: Washington
city: Milwaukee
country: United States
facility: Local Institution - 0065
state: Wisconsin
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Toronto
country: Canada
facility: Local Institution - 0092
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Children's Hospital of the MUHC
state: Quebec
city: Praha 5
country: Czechia
facility: Klinika detske hematologie a onkologie
city: Vandoeuvre lès Nancy
country: France
facility: Local Institution - 0034
state: Meurthe-et-Moselle
city: Lille cedex
country: France
facility: Local Institution - 0030
city: Lyon Cedex 08
country: France
facility: Local Institution - 0029
city: Marseille
country: France
facility: Local Institution - 0032
city: Nantes
country: France
facility: Local Institution - 0028
city: Paris
country: France
facility: Local Institution - 0031
city: Paris
country: France
facility: Local Institution - 0026
city: Toulouse cedex 9
country: France
facility: Local Institution - 0033
city: Villejuif
country: France
facility: Local Institution - 0027
city: Berlin
country: Germany
facility: Local Institution - 0056
city: Giessen
country: Germany
facility: Local Institution - 0055
city: Hannover
country: Germany
facility: Local Institution - 0057
city: Muenchen
country: Germany
facility: Local Institution - 0102
city: Dublin
country: Ireland
facility: Local Institution - 0017
city: Aviano (PN)
country: Italy
facility: Local Institution - 0024
city: Bologna
country: Italy
facility: Local Institution - 0020
city: Genova
country: Italy
facility: Local Institution - 0021
city: Monza (mb)
country: Italy
facility: Local Institution - 0019
city: Napoli
country: Italy
facility: Local Institution - 0023
city: Roma
country: Italy
facility: Local Institution - 0022
city: Rotterdam
country: Netherlands
facility: Local Institution - 0001
city: Utrecht
country: Netherlands
facility: Local Institution - 0006
city: Gdansk
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution - 0082
city: Madrid
country: Spain
facility: Local Institution - 0084
city: Leeds
country: United Kingdom
facility: Local Institution - 0035
state: North Yorkshire
city: Leeds
country: United Kingdom
facility: Local Institution
state: Yorkshire
city: Birmingham
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution - 0002
city: Manchester
country: United Kingdom
facility: Local Institution - 0012
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: