A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
- Conditions
- Lymphoma, Non-HodgkinChronic Lymphocytic Leukemia
- Interventions
- Drug: JNJ-64264681Drug: JNJ-67856633
- Registration Number
- NCT04657224
- Lead Sponsor
- Janssen Research & Development, LLC
- 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).
- Detailed 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after start of first subsequent antineoplastic therapy, after the clinical cut off (CCO) date participants will be withdrawn from the study 30 days after the last dose of study drugs were administered).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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 75
- 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
- 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])
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 JNJ-64264681 Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator. Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 JNJ-67856633 Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator. Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 JNJ-64264681 Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 JNJ-67856633 Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.
- Primary Outcome Measures
Name Time Method Part A: Number of Participants with Dose-limiting Toxicity (DLT) Up to 28 days 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.
Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Up to 3 years and 9 months 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.
- Secondary Outcome Measures
Name Time Method Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs) Up to 3 years and 9 months BTK occupancy will be assessed.
Overall Response Rate (ORR) Up to 3 years and 9 months ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM).
Plasma Concentrations of JNJ-64264681 and JNJ-67856633 Up to 3 years and 9 months Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed.
Time to First Response Up to 3 years and 9 months 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.
Duration of Response Up to 3 years and 9 months 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.
Trial Locations
- Locations (27)
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Monash Medical Centre
🇦🇺Clayton, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
Linear Clinical Research Ltd
🇦🇺Nedlands, Australia
AZ St.-Jan Brugge-Oostende AV
🇧🇪Brugge, Belgium
Scientia Clinical Research
🇦🇺Randwick, Australia
CHRU de Lille Hopital Claude Huriez
🇫🇷Lille, France
Universitair Ziekenhuis Gent - UZ GENT
🇧🇪Gent, Belgium
Chu Hotel Dieu
🇫🇷Nantes Cedex 1, France
Centre hospitalier Lyon-Sud
🇫🇷Pierre Benite, France
CHU Bretonneau
🇫🇷Tours Cedex 9, France
Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Pratia MCM Krakow
🇵🇱Krakow, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Skorzewo, Poland
Hosp Univ Fund Jimenez Diaz
🇪🇸Madrid, Spain
Medical Center of Limited Liability Company Arensia Exploratory Medicine
🇺🇦Kiev, Ukraine
Tel Aviv Sourasky MC
🇮🇱Tel Aviv, Israel
CHU UCL Namur - Site Godinne
🇧🇪Yvoir, Belgium
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of