Clinical trial NCT02581631: An Investigational Immuno-therapy Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas
Official title: A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination With Brentuximab Vedotin in Subjects With Relapsed Refractory Non Hodgkin Lymphomas With CD30 Expression (CheckMate 436: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 436)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2015-10-21
Enrollment: 145
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Nivolumab, in combination with brentuximab vedotin, is safe and effective in patients with certain subtypes of non-Hodgkin's lymphomas with CD30 expression that have not responded to treatment or have come back. The subtypes we are studying are Diffuse Large B-Cell Lymphoma (DLBCL), Peripheral T-Cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Primary Mediastinal Large B-Cell Lymphoma (PMBL) and Mediastinal Gray Zone Lymphoma (MGZL).


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Relapsed/refractory diffuse large B cell lymphoma (DLBCL), relapsed/refractory peripheral T cell lymphoma (PTCL) (all subtypes excluding anaplastic large cell lymphoma), relapsed/refractory Cutaneous T cell lymphoma (CTCL) mycosis fungoides/sezary syndrome (MF/SS), relapsed/refractory primary mediastinal B lymphoma (PMBL), and relapsed/refractory mediastinal gray zone lymphoma (MGZL)
* Expression of CD30
* Subjects must be 18 years or older (≥ 15 years for PMBL)

Exclusion Criteria:

* Known central nervous system (CNS) lymphomas; Active cerebral/meningeal disease related to the underlying malignancy
* Active, known, or suspected autoimmune disease

Primary outcomes:
measure: Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
timeFrame: From first dose of treatment to 6 weeks after first dose
measure: Safety Analysis - Number of Participant Deaths
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Number of Participants With Adverse Advents
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Number of Participants With Serious Adverse Events
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Number of Participants With Drug Related Adverse Events
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Safety Analysis - Percentage of Participants With Liver Test Abnormalities
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
measure: Objective Response Rate (ORR)
timeFrame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From the first patient first visit to 8 months after the last patient first visit (up to 48 months)
measure: Complete Response Rate (CRR)
timeFrame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)
measure: Duration of Complete Response
timeFrame: From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)
measure: Progression Free Survival (PFS)
timeFrame: From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months)
measure: Overall Survival (OS)
timeFrame: From the first patient first visit to 8 months after the last patient first visit (about 48 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0017
state: Alabama
city: Miami
country: United States
facility: University Of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0012
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute.
state: Georgia
city: Chicago
country: United States
facility: University Of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Local Institution - 0003
state: New York
city: New York
country: United States
facility: Local Institution - 0010
state: New York
city: Rochester
country: United States
facility: University Of Rochester
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Greenville
country: United States
facility: Bon Secours-St Francis Hosp
state: South Carolina
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0011
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre Benite Cedex
country: France
facility: Local Institution - 0020
city: Bergamo
country: Italy
facility: Local Institution - 0018
city: Bologna
country: Italy
facility: Local Institution - 0024
city: Rozzano (milano)
country: Italy
facility: Istituto Clinico Humanitas
city: Hospitalet de Llobregat - Barcelona
country: Spain
facility: Local Institution - 0027
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Zinzani PL, Santoro A, Gritti G, Brice P, Barr PM, Kuruvilla J, Cunningham D, Kline J, Johnson NA, Mehta-Shah N, Manley T, Francis S, Sharma M, Moskowitz AJ. Nivolumab Combined With Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Efficacy and Safety From the Phase II CheckMate 436 Study. J Clin Oncol. 2019 Nov 20;37(33):3081-3089. doi: 10.1200/JCO.19.01492. Epub 2019 Aug 9.