A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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). 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Part A: Dose escalation: JNJ-64264681 and 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. |
Drug: JNJ-64264681
JNJ-64264681 capsules will be administered orally.
Drug: JNJ-67856633
JNJ-67856633 capsules or tablets will be administered orally.
|
Experimental: Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. |
Drug: JNJ-64264681
JNJ-64264681 capsules will be administered orally.
Drug: JNJ-67856633
JNJ-67856633 capsules or tablets will be administered orally.
|
Outcome Measures
Primary Outcome Measures
- 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 2 years and 3 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
- Plasma Concentrations of JNJ-64264681 and JNJ-67856633 [Up to 2 years and 3 months]
Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed.
- Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs) [Up to 2 years and 3 months]
BTK occupancy will be assessed.
- Overall Response Rate (ORR) [Up to 2 years and 3 months]
ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM).
- Time to First Response [Up to 2 years and 3 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 2 years and 3 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
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Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds
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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)
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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:
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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
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Known (active) central nervous system (CNS) involvement
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Received prior solid organ transplantation
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Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients
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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])
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
2 | Monash Medical Centre | Clayton | Australia | 3168 | |
3 | Peter MacCallum Cancer Centre | Melbourne | Australia | 3000 | |
4 | Linear Clinical Research Ltd | Nedlands | Australia | 6009 | |
5 | Scientia Clinical Research | Randwick | Australia | 2031 | |
6 | AZ St.-Jan Brugge-Oostende AV | Brugge | Belgium | 8000 | |
7 | Universitair Ziekenhuis Gent - UZ GENT | Gent | Belgium | 9000 | |
8 | CHU UCL Namur - Site Godinne | Yvoir | Belgium | 5530 | |
9 | CHRU de Lille - Hôpital Claude Huriez | Lille | France | 59037 | |
10 | Chu Hotel Dieu | Nantes Cedex 1 | France | 44093 | |
11 | Centre hospitalier Lyon-Sud | Pierre Benite | France | 69495 | |
12 | CHU Bretonneau | Tours Cedex 9 | France | 37044 | |
13 | Arensia Exploratory Medicine | Tbilisi | Georgia | 0112 | |
14 | Hadassah Medical Center | Jerusalem | Israel | 9112001 | |
15 | Sheba Medical Center | Ramat Gan | Israel | 52621 | |
16 | Tel Aviv Sourasky MC | Tel Aviv | Israel | 6423906 | |
17 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
18 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
19 | Seoul National University Hospital | Seoul | Korea, Republic of | 3080 | |
20 | Arensia Exploratory Medicine | Chisinau | Moldova, Republic of | Md2025 | |
21 | Academic Medical Center | Amsterdam | Netherlands | 1105 AZ | |
22 | Uniwersyteckie Centrum Kliniczne | Gdansk | Poland | 80-214 | |
23 | Pratia Onkologia Katowice | Katowice | Poland | 40-519 | |
24 | Pratia MCM Krakow | Krakow | Poland | 30-510 | |
25 | Centrum Medyczne Pratia Poznan | Skorzewo | Poland | 60-185 | |
26 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
27 | Hosp. Univ. Fund. Jimenez Diaz | Madrid | Spain | 28040 | |
28 | Medical Center of Limited Liability Company Arensia Exploratory Medicine | Kiev | Ukraine | 1135 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trials, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108877
- 2020-003149-12
- 64264681LYM1002