An Investigational Immuno-therapy Safety and Effectivenes... | NCT02581631 | Trialant
NCT02581631
Sponsor
Bristol-Myers Squibb
Status
Completed
Last Update Posted
Mar 7, 2023Actual
Enrollment
145Actual
Phase
Phase 1Phase 2
Conditions
Non-Hodgkin's Disease
Interventions
Nivolumab
Brentuximab Vedotin
Countries
United States
Canada
France
Italy
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02581631
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CA209-436
Secondary IDs
ID
Type
Description
Link
2015-003286-28
EudraCT Number
Brief Title
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)
Acronym
CheckMate 436
Organization
Bristol-Myers SquibbINDUSTRY
Status Module
Record Verification Date
Feb 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 11, 2016Actual
Primary Completion Date
Jan 16, 2020Actual
Completion Date
Feb 7, 2022Actual
First Submitted Date
Oct 13, 2015
First Submission Date that Met QC Criteria
Oct 19, 2015
First Posted Date
Oct 21, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 15, 2021
Results First Submitted that Met QC Criteria
Feb 7, 2023
Results First Posted Date
Mar 7, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 7, 2023
Last Update Posted Date
Mar 7, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Bristol-Myers SquibbINDUSTRY
Collaborators
Name
Class
Seagen Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
Detailed Description
Not provided
Conditions Module
Conditions
Non-Hodgkin's Disease
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
145Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Nivolumab+Brentuximab Vedotin
Experimental
Nivolumab+Brentuximab Vedotin dose as specified
Biological: Nivolumab
Drug: Brentuximab Vedotin
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Nivolumab
Biological
Nivolumab+Brentuximab Vedotin
Brentuximab Vedotin
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.
From first dose of treatment to 6 weeks after first dose
Safety Analysis - Number of Participants With Adverse Advents
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.
Safety Analysis - Number of Participants With Serious Adverse Events
A Serious Adverse Event (SAE) is 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
DOR will be calculated from the date of initial documentation of a response (CR, or PR) to 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 occurs first.
DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria.
CTCL complete and partial response are defined in The consensus Global Response Score assessment.
Other Outcomes
Not provided
Eligibility Module
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
15 Years
Maximum Age
Not provided
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Bristol-Myers Squibb
Bristol-Myers Squibb
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Local Institution - 0017
Birmingham
Alabama
35294-3300
United States
University Of Miami Sylvester Comprehensive Cancer Center
The Dose Evaluation Phase (Cohort A) will include a dose limiting toxicity (DLT) evaluation for the dose level of brentuximab vedotin 1.8 mg/kg in combination with nivolumab 240 mg. The reduced dose of brentuximab vedotin at 1.2 mg/kg was not needed based on the safety data reviewed throughout the DLT evaluation period.
The percentage of participants with a best overall response (BOR) of CR or PR.
DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria.
CTCL complete and partial response are defined in The consensus Global Response Score assessment.
From the first patient first visit to 8 months after the last patient first visit (up to 48 months)
Complete Response Rate (CRR)
The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants.
DLBCL, PTCL, PMBL & MGZL (CR)
1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)
100% clearance of skin lesions.
all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
organs should not be enlarged on examination or imaging
absence of blood involvement
From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)
Duration of Complete Response
The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first.
DLBCL, PTCL, PMBL & MGZL (CR)
1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)
100% clearance of skin lesions.
all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
organs should not be enlarged on examination or imaging
absence of blood involvement
From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)
Progression Free Survival (PFS)
PFS is defined as the time from the date of 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. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy.
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)
Overall Survival (OS)
OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.
From the first patient first visit to 8 months after the last patient first visit (about 48 months)
Miami
Florida
33136
United States
Local Institution - 0012
Tampa
Florida
33612
United States
Winship Cancer Institute.
Atlanta
Georgia
30322
United States
University Of Chicago
Chicago
Illinois
60637
United States
Mayo Clinic
Rochester
Minnesota
55905
United States
Washington University School Of Medicine
St Louis
Missouri
63110
United States
Local Institution - 0003
New York
New York
10021
United States
Local Institution - 0010
New York
New York
10029
United States
University Of Rochester
Rochester
New York
14642
United States
Levine Cancer Institute
Charlotte
North Carolina
28204
United States
The Ohio State University Comprehensive Cancer Center
Columbus
Ohio
43210
United States
Stephenson Cancer Center
Oklahoma City
Oklahoma
73104
United States
Providence Portland Medical Center
Portland
Oregon
97213
United States
Bon Secours-St Francis Hosp
Greenville
South Carolina
29607
United States
University of Washington - Seattle Cancer Care Alliance
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.
Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.
DLT evaluable Participants
Posted
Count of Participants
Participants
From first dose of treatment to 6 weeks after first dose
Safety Analysis - Number of Participants With Adverse Advents
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.
Safety Analysis - Number of Participants With Serious Adverse Events
A Serious Adverse Event (SAE) is 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
The percentage of participants with a best overall response (BOR) of CR or PR.
DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria.
CTCL complete and partial response are defined in The consensus Global Response Score assessment.
DOR will be calculated from the date of initial documentation of a response (CR, or PR) to 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 occurs first.
DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria.
CTCL complete and partial response are defined in The consensus Global Response Score assessment.
All Treated Participants who achieve a partial response or complete response
Posted
Median
95% Confidence Interval
Months
From the first patient first visit to 8 months after the last patient first visit (up to 48 months)
The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants.
DLBCL, PTCL, PMBL & MGZL (CR)
1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)
100% clearance of skin lesions.
all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
organs should not be enlarged on examination or imaging
absence of blood involvement
All Treated Participants
Posted
Number
Percentage of Participants
From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)
The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first.
DLBCL, PTCL, PMBL & MGZL (CR)
1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)
100% clearance of skin lesions.
all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
organs should not be enlarged on examination or imaging
absence of blood involvement
All Treated Participants who achieved a complete response
Posted
Median
95% Confidence Interval
Months
From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)
PFS is defined as the time from the date of 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. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy.
All Treated Participants
Posted
Median
95% Confidence Interval
Months
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)
OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.
All Treated Participants
Posted
Median
95% Confidence Interval
Months
From the first patient first visit to 8 months after the last patient first visit (about 48 months)
Safety Analysis - Number of Participant Deaths - Extended Collection
Number of participant Deaths
This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
All Treated Participants
Posted
Count of Participants
Participants
from first date of treatment to final database lock. Approximately 6 years and 7 months.
Safety Analysis - Number of Participants With Adverse Events - Extended Collection
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.
This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
All Treated Participants
Posted
Count of Participants
Participants
From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
Safety Analysis - Number of Participants With Serious Adverse Events - Extended Collection
A Serious Adverse Event (SAE) is 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 This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
All Treated Participants
Posted
Count of Participants
Participants
From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation - Extended Collection
Number of Adverse events leading to discontinuation
This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
All Treated Participants
Posted
Count of Participants
Participants
From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
Safety Analysis - Number of Participants With Drug Related Adverse Events - Extended Collection
Number of Drug Related Adverse Events
This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
All Treated Participants
Posted
Count of Participants
Participants
From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
From first patient first visit to first to final data base lock. Approximately 6 years and 7 months. All cause mortality is calculated from first treatment to final data base lock.. Approximately 6 years and 7 months.
OG00226.97(2.79 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, the upper limit number is simply undefined, and denoted as NA.
OG00320.76(1.22 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, the upper limit number is simply undefined, and denoted as NA.
OG004NA(23.33 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, then median DOR and upper limit number is simply undefined, and denoted as NA.
OG00036.53(9.92 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, upper limit number is simply undefined, and denoted as NA.
OG0017.39(2.17 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, upper limit number is simply undefined, and denoted as NA.
OG002NA(NA to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, then median DOR and upper limit number is simply undefined, and denoted as NA.
OG003NA(NA to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, then median DOR, lower limit number and upper limit number is simply undefined, and denoted as NA.
OG004NA(27.89 to NA)The median DOR is defined to be the time at which 50% of treated participants achieved a response. If the number of responders doesn't reach 50% at the end of the available data, then median DOR and upper limit number is simply undefined, and denoted as NA.