A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL
Study Details
Study Description
Brief 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) in Part A (Dose Escalation) and to evaluate safety of JNJ-67856633 and ibrutinib in combination, at the RP2D regimen in Part B (Cohort Expansion).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed 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 study will be conducted in 2 parts: Part A (Dose Escalation) and Part B (Expansion Phase). In dose escalation phase, one or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633 will be determined. After the RP2D(s) is determined in the dose escalation phase, expansion phase will be conducted. 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 6 months.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: JNJ-67856633 and Ibrutinib Participants in Part A (dose escalation) will receive JNJ-67856633 together with Ibrutinib orally on a 21-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) has been identified. Participants in Part B (cohort expansion) will receive JNJ-67856633 together with Ibrutinib orally at one of the RP2D(s) determined in Part A. |
Drug: JNJ-67856633
Participants will receive JNJ-67856633 orally.
Drug: Ibrutinib
Participants will receive Ibrutinib orally.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Percentage of Participants with Dose-Limiting Toxicity (DLT) [Up to 21 days]
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.
- Percentage of Participants with Adverse Events (AEs) by Severity [Up to 2 years and 6 months]
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Secondary Outcome Measures
- Part A and B: Plasma Concentration of JNJ-67856633 and Ibrutinib [Up to 2 years and 6 months]
Plasma samples will be analyzed to determine concentrations of JNJ-67856633 and Ibrutinib.
- Part B: Duration of Response (DOR) [Up to 2 years and 6 months]
DOR is defined for participants who achieved PR, MaRR or CR as the time between the date of initial documentation of such responses to the date of either the first documented evidence of relapse or death. For participants who have not relapsed or died, data will be censored at the last disease evaluation.
- Part B: Time to First Response (TTR) [Up to 2 years and 6 months]
TTR is defined for participants who achieved PR, MaRR, or CR as the time from the first dose of study drug to first of such responses.
- Part B: Overall Response Rate (ORR) [Up to 2 years and 6 months]
ORR is defined as the percentage of participants who have a partial response (PR) and complete response (CR) according to Non-Hodgkin Lymphoma (NHL), International Workshop on Chronic Lymphocytic Leukemia (iwCLL) and Waldenstrom macroglobulinemia (WM) response criteria.
- Part B: Complete Response Rate [Up to 2 years and 6 months]
Complete response rate is defined as the percentage of participants who achieve a best response of CR according to the iwCLL, NHL and WM response criteria.
- Part B: Major Response Rate (MaRR) [Up to 2 years and 6 months]
MaRR (PR+ very good partial response [VGPR]) rate is defined as the percentage of participants who achieve a best response of PR or VGPR according to NHL, iwCLL and WM response criteria.
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 specified range
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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
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Willing and able to adhere to the lifestyle restrictions specified in this protocol
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Participants must have tumor tissue availability
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Adequate organ functions
Exclusion Criteria:
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Known (active) Central Nervous System (CNS) involvement
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Prior treatment with JNJ-67856633 or another MALT1 inhibitor that is associated with disease progression or intolerable toxicities
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
2 | Aarhus University Hospital | Aarhus | Denmark | 8200 | |
3 | Rigshospitalet | Copenhagen | Denmark | 2100 | |
4 | CHRU de Lille - Hôpital Claude Huriez | Lille | France | 59037 | |
5 | Institut Paoli Calmettes | Marseille | France | 13009 | |
6 | CHU de Nantes hôtel-Dieu | Nantes | France | 44000 | |
7 | Hopital St Louis | Paris | France | 75475 | |
8 | CHU de Bordeaux - Hôpital Haut-Lévêque | Pessac | France | 33600 | |
9 | Hopital Pontchaillou | Rennes | France | 35000 | |
10 | Gustave Roussy | Villejuif Cedex | France | 94800 | |
11 | Alexandra General Hospital of Athens | Athens | Greece | 11528 | |
12 | Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna | Bologna | Italy | 40138 | |
13 | Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico | Milano | Italy | 20122 | |
14 | IRCCS Ospedale San Raffaele | Milano | Italy | 20132 | |
15 | ASST Grande Ospedale Metropolitano Niguarda | Milano | Italy | 20162 | |
16 | Fondazione IRCCS Policlinico San Matteo | Pavia | Italy | 27100 | |
17 | Inje University Busan Paik Hospital | Busan | Korea, Republic of | 47392 | |
18 | Chonnam National University Hwasun Hospital | Jeollanam-do | Korea, Republic of | 58128 | |
19 | The Catholic University of Korea Yeouido St. Mary's Hospital | Seoul | Korea, Republic of | 07345 | |
20 | Pratia MCM Krakow | Krakow | Poland | 30-510 | |
21 | Centrum Medyczne Pratia Poznan | Skorzewo | Poland | 60-185 | |
22 | Hosp. Univ. Germans Trias I Pujol | Badalona, Barcelona | Spain | 8916 | |
23 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
24 | Hosp. Clinic I Provincial de Barcelona | Barcelona | Spain | 08036 | |
25 | Hosp. Univ. Infanta Leonor | Madrid | Spain | 28031 | |
26 | Hosp. Clinico Univ. de Salamanca | Salamanca | Spain | 37007 | |
27 | Universitetssjukhuset Lund, Onkologiska Kliniken, Lund | Lund | Sweden | 221 85 | |
28 | University College Hospital | London | United Kingdom | NW1 2PG |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109010
- 2021-000191-12
- 67856633LYM1002