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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04657224
• Other study ID #: CR108877
• Secondary ID: 2020-003149-1264
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 25, 2021
• Est. completion date: July 11, 2025

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 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: July 11, 2025
• Est. primary completion date: July 11, 2025
• 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 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])

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-64264681
JNJ-64264681 capsules will be administered orally.
• JNJ-67856633
JNJ-67856633 capsules or tablets will be administered orally.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	Linear Clinical Research Ltd	Nedlands
Australia	Scientia Clinical Research	Randwick
Belgium	AZ St.-Jan Brugge-Oostende AV	Brugge
Belgium	Universitair Ziekenhuis Gent - UZ GENT	Gent
Belgium	CHU UCL Namur - Site Godinne	Yvoir
France	CHRU de Lille Hopital Claude Huriez	Lille
France	Chu Hotel Dieu	Nantes Cedex 1
France	Centre hospitalier Lyon-Sud	Pierre Benite
France	CHU Bretonneau	Tours Cedex 9
Georgia	Arensia Exploratory Medicine	Tbilisi
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky MC	Tel Aviv
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Moldova, Republic of	Arensia Exploratory Medicine	Chisinau
Netherlands	Academic Medical Center	Amsterdam
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Krakow	Krakow
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Ukraine	Medical Center of Limited Liability Company Arensia Exploratory Medicine	Kiev
United States	Stony Brook University Medical Center	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Georgia,  Israel,  Korea, Republic of,  Moldova, Republic of,  Netherlands,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Plasma Concentrations of JNJ-64264681 and JNJ-67856633	Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed.	Up to 3 years and 9 months
Secondary	Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)	BTK occupancy will be assessed.	Up to 3 years and 9 months
Secondary	Overall Response Rate (ORR)	ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM).	Up to 3 years and 9 months
Secondary	Time to First Response	Time to first response defined for the responders as the time from the date of first dose of study treatment to the date of initial documentation of a first response as defined in the disease-specific response criteria.	Up to 3 years and 9 months
Secondary	Duration of Response	DOR will be calculated from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.	Up to 3 years and 9 months