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

NCT04657224 | Completed Phase 1 FDA Drug

• 4 other identifiers: CR10887764264681LYM10022020-003149-122024-512687-66-00
• Study Type: interventional
• Target: 75
• Locations: 12 countries
• Sites: 28

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).

Conditions

Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Part A: Number of Participants with Dose-limiting Toxicity (DLT)

  Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

  Up to 28 days

• Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

  Up to 3 years and 9 months

Secondary Outcomes (5)

• Plasma Concentrations of JNJ-64264681 and JNJ-67856633

  Up to 3 years and 9 months

• Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)

  Up to 3 years and 9 months

• Overall Response Rate (ORR)

  Up to 3 years and 9 months

• Time to First Response

  Up to 3 years and 9 months

• Duration of Response

  Up to 3 years and 9 months

Study Arms (2)

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

EXPERIMENTAL

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

Drug: JNJ-64264681; Drug: JNJ-67856633

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

EXPERIMENTAL

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

Drug: JNJ-64264681; Drug: JNJ-67856633

Interventions

JNJ-64264681 DRUG

JNJ-64264681 capsules will be administered orally.

Part A: Dose escalation: JNJ-64264681 and JNJ-67856633; Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633

JNJ-67856633 DRUG

JNJ-67856633 capsules or tablets will be administered orally.

Part A: Dose escalation: JNJ-64264681 and JNJ-67856633; Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \[Grade 1\])

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (28)

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Monash Medical Centre

Clayton, 3168, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Linear Clinical Research Ltd

Nedlands, 6009, Australia

Location

Scientia Clinical Research

Randwick, 2031, Australia

Location

AZ St.-Jan Brugge-Oostende AV

Bruges, 8000, Belgium

Location

Universitair Ziekenhuis Gent - UZ GENT

Ghent, 9000, Belgium

Location

CHU UCL Namur - Site Godinne

Yvoir, 5530, Belgium

Location

CHRU de Lille Hopital Claude Huriez

Lille, 59037, France

Location

Chu Hotel Dieu

Nantes, 44093, France

Location

Centre hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

CHU Bretonneau

Tours, 37044, France

Location

Arensia Exploratory Medicine

Tbilisi, 0112, Georgia

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky MC

Tel Aviv, 6423906, Israel

Location

Arensia Exploratory Medicine

Chisinau, Md2025, Moldova

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 214, Poland

Location

Pratia Onkologia Katowice

Katowice, 40 519, Poland

Location

Pratia MCM Krakow

Krakow, 30-727, Poland

Location

Centrum Medyczne Pratia Poznan

Skorzewo, 60 185, Poland

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Medical Center of Limited Liability Company Arensia Exploratory Medicine

Kyiv, 01135, Ukraine

Location

MeSH Terms

Conditions

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

Interventions

JNJ-64264681

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janssen Research & Development, LLC Clinical Trials

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: February 25, 2021
• Primary Completion: January 16, 2025
• Study Completion: January 16, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); NL (1); KR (3); PL (4); ES (2); MO (1); GE (1); IL (3); FR (4); UA (1); US (1); BE (3)