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

A Phase 1b Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: JNJ-67856633; Drug: Ibrutinib

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• France
  • Lille, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44000
    • CHU de Nantes hotel Dieu
  • Paris, France, 75475
    • Hopital St Louis
  • Pessac, France, 33600
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Villejuif Cedex, France, 94800
    • Gustave Roussy
• Poland
  • Krakow, Poland, 30-727
    • Pratia MCM Krakow
  • Skorzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznan
• Sweden
  • Lund, Sweden, 221 85
    • Universitetssjukhuset Lund, Onkologiska Kliniken, Lund

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: JNJ-67856633; Participants will receive JNJ-67856633 orally.; Drug: Ibrutinib; Participants will receive Ibrutinib orally.; Other Names: JNJ-54179060

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Dose-Limiting Toxicity (DLT)	Percentage of Participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematological toxicity or hematological toxicity.	Up to 21 days
Percentage of Participants with Adverse Events (AEs) by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Up to 2 years and 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of JNJ-67856633 and Ibrutinib	Plasma samples will be analyzed to determine concentrations of JNJ-67856633 and Ibrutinib.	Up to 2 years and 9 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Estimated): November 25, 2024
• Study Completion (Estimated): November 25, 2024

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Ibrutinib
• Other Study ID Numbers: CR109010; 2021-000191-12 (EudraCT Number); 67856633LYM1002 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No