A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

NCT ID: NCT04657224

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-25
• Study Completion Date: 2025-01-16

Brief Summary

The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).

Detailed Description

Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than 60 subtypes have been identified and classified by the world health organization. JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28 days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal of consent, death, 6 months after start of first subsequent antineoplastic therapy, after the clinical cut off (CCO) date participants will be withdrawn from the study 30 days after the last dose of study drugs were administered). The total study duration is estimated at 2 years and 2 months. Safety assessments will include physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, eastern cooperative oncology group performance status, echocardiogram, and adverse events monitoring.

Conditions

Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia

Study Design

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

Study Groups

Part A: Dose escalation: JNJ-64264681 and JNJ-67856633

Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator.

Group Type: EXPERIMENTAL

JNJ-64264681

Intervention Type: DRUG

JNJ-64264681 capsules will be administered orally.

JNJ-67856633

Intervention Type: DRUG

JNJ-67856633 capsules or tablets will be administered orally.

Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633

Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.

Group Type: EXPERIMENTAL

JNJ-64264681

Intervention Type: DRUG

JNJ-64264681 capsules will be administered orally.

JNJ-67856633

Intervention Type: DRUG

JNJ-67856633 capsules or tablets will be administered orally.

Interventions

JNJ-64264681

JNJ-64264681 capsules will be administered orally.

Intervention Type: DRUG

JNJ-67856633

JNJ-67856633 capsules or tablets will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds
• Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available at baseline as described in the protocol. This is not required for participants with chronic lymphocytic leukemia (CLL)
• Women of childbearing potential must agree to use a barrier method of contraception; use a highly effective preferably user-independent method of contraception; not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; not to plan to become pregnant; and not to breast-feed

Exclusion Criteria

• Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK) or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without evidence of progression or intolerable class-related toxicity will be eligible
• Known (active) central nervous system (CNS) involvement
• Received prior solid organ transplantation
• Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients
• Toxicities from previous anti-cancer therapies that have not resolved to baseline levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade 2] and peripheral neuropathy [Grade 1])

• 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 Trials

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Stony Brook University Medical Center

Stony Brook, New York, United States

Monash Medical Centre

Clayton, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

Linear Clinical Research Ltd

Nedlands, , Australia

Scientia Clinical Research

Randwick, , Australia

AZ St.-Jan Brugge-Oostende AV

Bruges, , Belgium

Universitair Ziekenhuis Gent - UZ GENT

Ghent, , Belgium

CHU UCL Namur - Site Godinne

Yvoir, , Belgium

CHRU de Lille Hopital Claude Huriez

Lille, , France

Chu Hotel Dieu

Nantes, , France

Centre hospitalier Lyon-Sud

Pierre-Bénite, , France

CHU Bretonneau

Tours, , France

Arensia Exploratory Medicine

Tbilisi, , Georgia

Hadassah Medical Center

Jerusalem, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Tel Aviv Sourasky MC

Tel Aviv, , Israel

Arensia Exploratory Medicine

Chisinau, , Moldova

Academic Medical Center

Amsterdam, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Pratia Onkologia Katowice

Katowice, , Poland

Pratia MCM Krakow

Krakow, , Poland

Centrum Medyczne Pratia Poznan

Skorzewo, , Poland

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Medical Center of Limited Liability Company Arensia Exploratory Medicine

Kyiv, , Ukraine

Countries

United States; Australia; Belgium; France; Georgia; Israel; Moldova; Netherlands; Poland; South Korea; Spain; Ukraine

Other Identifiers

64264681LYM1002

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003149-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-512687-66-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR108877

Identifier Type: -

Identifier Source: org_study_id