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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04876092
• Other study ID #: CR109010
• Secondary ID: 2021-000191-1267
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 28, 2021
• Est. completion date: November 25, 2024

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: November 25, 2024
• Est. primary completion date: November 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• JNJ-67856633
Participants will receive JNJ-67856633 orally.
• Ibrutinib
Participants will receive Ibrutinib orally.

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
France	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 Cedex
Poland	Pratia MCM Krakow	Krakow
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Sweden	Universitetssjukhuset Lund, Onkologiska Kliniken, Lund	Lund

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Denmark,  France,  Poland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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