A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04876092
Collaborator
(none)
100
28
1
33.1
3.6
0.1

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
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

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Actual Study Start Date :
Jul 28, 2021
Anticipated Primary Completion Date :
Feb 21, 2023
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
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:
  • JNJ-54179060
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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

    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 specified range

    • 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

    • Willing and able to adhere to the lifestyle restrictions specified in this protocol

    • Participants must have tumor tissue availability

    • Adequate organ functions

    Exclusion Criteria:
    • Known (active) Central Nervous System (CNS) involvement

    • 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.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT04876092
    Other Study ID Numbers:
    • CR109010
    • 2021-000191-12
    • 67856633LYM1002
    First Posted:
    May 6, 2021
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jul 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 Jul 15, 2022