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

Phase 1
Completed
Conditions
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Interventions
Registration Number
NCT04876092
Lead Sponsor
Janssen Research & Development, LLC
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
JNJ-67856633 and IbrutinibJNJ-67856633Participants 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).
JNJ-67856633 and IbrutinibIbrutinibParticipants 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).
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Dose-Limiting Toxicity (DLT)Up to 21 days

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.

Percentage of Participants with Adverse Events (AEs) by SeverityUp to 2 years and 9 months

Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Secondary Outcome Measures
NameTimeMethod
Plasma Concentration of JNJ-67856633 and IbrutinibUp to 2 years and 9 months

Plasma samples will be analyzed to determine concentrations of JNJ-67856633 and Ibrutinib.

Trial Locations

Locations (10)

Institut Paoli Calmettes

🇫🇷

Marseille, France

Hopital St Louis

🇫🇷

Paris, France

Rigshospitalet

🇩🇰

Copenhagen, Denmark

CHU de Nantes hotel Dieu

🇫🇷

Nantes, France

CHRU de Lille Hopital Claude Huriez

🇫🇷

Lille, France

Gustave Roussy

🇫🇷

Villejuif Cedex, France

CHU de Bordeaux - Hospital Haut-Leveque

🇫🇷

Pessac, France

Universitetssjukhuset Lund, Onkologiska Kliniken, Lund

🇸🇪

Lund, Sweden

Pratia MCM Krakow

🇵🇱

Krakow, Poland

Centrum Medyczne Pratia Poznan

🇵🇱

Skorzewo, Poland

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