A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL

NCT ID: NCT04876092

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-28
• Study Completion Date: 2025-02-13

Brief Summary

The purpose of this study is to determine the safety and recommended Phase 2 dose (RP2D) of JNJ-67856633 and ibrutinib in combination in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Detailed Description

Non-Hodgkin lymphoma (NHL) represents the most frequent hematologic malignancy in the world and represents a diverse set of diseases. JNJ-67856633-ZAF (referred as JNJ-67856633) is an orally bioavailable, potent, and selective first-in-class mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) inhibitor. JNJ-67856633 binds to an allosteric site on MALT1 with a mixed-type mechanism. Ibrutinib is a first-in-class, orally administered, potent, orally administered covalently binding small-molecule inhibitor of Bruton's tyrosine kinase (BTK), as well as interleukin-2-inducible kinase (ITK), a tyrosine protein (Tec) kinase family member present in T cells. The doses will be escalated in the study and one or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633 will be determined. The study is divided into 3 periods: a screening phase, a treatment phase, and a post-treatment follow-up phase. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy etc. Safety assessment like physical examination, vital signs, electrocardiogram (ECG), eastern cooperative oncology group (ECOG) performance status, and adverse events monitoring will be performed during the study. Total duration of the study will be up to 2 years and 9 months.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

JNJ-67856633 and Ibrutinib

Participants will receive JNJ-67856633 together with Ibrutinib orally on a 21-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET).

Group Type: EXPERIMENTAL

JNJ-67856633

Intervention Type: DRUG

Participants will receive JNJ-67856633 orally.

Ibrutinib

Intervention Type: DRUG

Participants will receive Ibrutinib orally.

Interventions

JNJ-67856633

Participants will receive JNJ-67856633 orally.

Intervention Type: DRUG

Ibrutinib

Participants will receive Ibrutinib orally.

Intervention Type: DRUG

Other Intervention Names

JNJ-54179060

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Cardiac parameters within the specified range
• Women of childbearing potential must agree to all of the following during the study and for 3 months after the last dose of study drug: a) use a barrier method of contraception; b) use a highly effective contraceptive methods; c) not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; d) not to plan to become pregnant; e) not to breast-feed
• Willing and able to adhere to the lifestyle restrictions specified in this protocol
• Participants must have tumor tissue availability
• Adequate organ functions

Exclusion Criteria

• Known (active) Central Nervous System (CNS) involvement
• Prior treatment with JNJ-67856633 or another MALT1 inhibitor that is associated with disease progression or intolerable toxicities

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Rigshospitalet

Copenhagen, , Denmark

CHRU de Lille Hopital Claude Huriez

Lille, , France

Institut Paoli Calmettes

Marseille, , France

CHU de Nantes hotel Dieu

Nantes, , France

Hopital St Louis

Paris, , France

CHU de Bordeaux - Hospital Haut-Leveque

Pessac, , France

Gustave Roussy

Villejuif, , France

Pratia MCM Krakow

Krakow, , Poland

Centrum Medyczne Pratia Poznan

Skorzewo, , Poland

Universitetssjukhuset Lund, Onkologiska Kliniken, Lund

Lund, , Sweden

Countries

Denmark; France; Poland; Sweden

Other Identifiers

67856633LYM1002

Identifier Type: OTHER

Identifier Source: secondary_id

2021-000191-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-512689-32-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109010

Identifier Type: -

Identifier Source: org_study_id