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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04657224
Collaborator
(none)
75
28
2
45.5
2.7
0.1

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
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

Study Type:
Interventional
Actual Enrollment :
75 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 25, 2021
Anticipated Primary Completion Date :
Jul 30, 2024
Anticipated Study Completion Date :
Dec 12, 2024

Arms and Interventions

Arm Intervention/Treatment
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

  1. 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.

  2. 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

  1. 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.

  2. Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs) [Up to 2 years and 3 months]

    BTK occupancy will be assessed.

  3. 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).

  4. 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.

  5. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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])

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT04657224
Other Study ID Numbers:
  • CR108877
  • 2020-003149-12
  • 64264681LYM1002
First Posted:
Dec 8, 2020
Last Update Posted:
Aug 22, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 22, 2022