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An Investigational Immuno-therapy Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas (CheckMate 436)

Primary Purpose

Non-Hodgkin's Disease

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Nivolumab

Brentuximab Vedotin

About this trial

This is an interventional treatment trial for Non-Hodgkin's Disease

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nivolumab+Brentuximab Vedotin

Arm Description

Nivolumab+Brentuximab Vedotin dose as specified

Outcomes

Primary Outcome Measures

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.

Safety Analysis - Number of Participant Deaths

Number of participant Deaths

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 is a congenital anomaly/birth defect is an important medical event

Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation

Number of participants with adverse events leading to discontinuation

Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction

Number of participants with adverse events leading to dose delay or reduction

Safety Analysis - Number of Participants With Drug Related Adverse Events

Number of participants with Drug Related Adverse Events

Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities

Percentage of participants with specific thyroid test abnormalities

Safety Analysis - Percentage of Participants With Liver Test Abnormalities

Percentage of participants with specific Liver test abnormalities

Objective Response Rate (ORR)

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.

Secondary Outcome Measures

Duration of Response (DOR)

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.

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

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

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.

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.

Full Information

NCT ID

NCT02581631

First Posted

October 13, 2015

Last Updated

February 7, 2023

Sponsor

Bristol-Myers Squibb

Collaborators

Seagen Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02581631

Brief Title

An Investigational Immuno-therapy Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas

Acronym

CheckMate 436

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

February 11, 2016 (Actual)

Primary Completion Date

January 16, 2020 (Actual)

Study Completion Date

February 7, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

Collaborators

Seagen Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Hodgkin's Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

145 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nivolumab+Brentuximab Vedotin

Arm Type

Experimental

Arm Description

Nivolumab+Brentuximab Vedotin dose as specified

Intervention Type

Biological

Intervention Name(s)

Nivolumab

Intervention Type

Drug

Intervention Name(s)

Brentuximab Vedotin

Primary Outcome Measure Information:

Title

Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase

Description

Time Frame

From first dose of treatment to 6 weeks after first dose

Title

Safety Analysis - Number of Participant Deaths

Description

Number of participant Deaths

Time Frame