Clinical Trials /

A Study of JNJ-67856633 in Participants With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

NCT03900598

Description:

The purpose of this study is to determine the recommended Phase 2 dose regimen or the maximum tolerated dose of JNJ-67856633 in participants with relapsed/ refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of JNJ-67856633 in Participants With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
  • Official Title: A Phase 1, First-in-Human, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-67856633, an Inhibitor of MALT1, in Participants With NHL and CLL

Clinical Trial IDs

  • ORG STUDY ID: CR108587
  • SECONDARY ID: 2018-003549-40
  • SECONDARY ID: 67856633LYM1001
  • NCT ID: NCT03900598

Conditions

  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
JNJ-67856633Part 1 (Dose Escalation): JNJ-67856633

Purpose

The purpose of this study is to determine the recommended Phase 2 dose regimen or the maximum tolerated dose of JNJ-67856633 in participants with relapsed/ refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.

Detailed Description

      Non-Hodgkin lymphoma (NHL) represents a diverse set of diseases. Among them diffuse large
      B-cell lymphoma (DLBCL) represents the most common subtype of NHL, accounting for 30 percent
      (%) to 40% of all newly diagnosed cases. Mucosa-associated lymphoid tissue lymphoma
      translocation protein 1 (MALT1) is a key mediator of the nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway and has been
      shown to play a critical role in different types of lymphoma, including activated B cell-like
      (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). JNJ-67856633 is a MALT1 inhibitor and
      will be administered orally. The study will evaluate the following: Dose Escalation (Part 1):
      One or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633. Cohort Expansion (Part 2):
      JNJ-67856633 is well tolerated and achieves antitumor responses at the RP2D. The study
      consists of screening phase (less than or equal to 28 days before first dose), treatment
      phase (from Cycle 1 Day 1 till end of treatment visit [within 30 (+7) days after the last
      dose]) and post-treatment phase. The total study duration will be approximately 3 years.
      Efficacy assessments will include radiographic image assessments, positron emission
      tomography scan, bone marrow assessment, endoscopy or colonoscopy etc. Safety will be
      monitored throughout the study.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 (Dose Escalation): JNJ-67856633ExperimentalParticipants will receive JNJ-67856633 until disease progression, intolerable toxicity, withdrawal of consent, or the investigator or sponsor decision. Subsequent dose levels will be assigned by the sponsor using an adaptive dose escalation strategy based on all available safety, pharmacokinetic (PK), and biomarker data.
  • JNJ-67856633
Part 2 (Cohort Expansion): JNJ-67856633ExperimentalParticipants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.
  • JNJ-67856633

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

          -  Cardiac parameters within the following range: corrected QT interval (QTc intervals
             corrected using Fridericia's formula [QTcF]) less than or equal to (<=)480
             milliseconds based on the average of triplicate assessments performed no more than 5
             minutes apart (plus minus [+-]3 minutes)

          -  Women of childbearing potential must have a negative highly sensitive serum (Beta
             human chorionic gonadotropin) at screening and prior to the first dose of study drug,
             and until 30 days after the last dose

          -  In addition to the user-independent, highly effective method of contraception, a male
             or female condom with or without spermicide is required, example, condom with
             spermicidal foam/gel/film/cream/suppository. Male condom and female condom should not
             be used together (due to risk of failure with friction)

          -  Men must wear a condom when engaging in any activity that allows for passage of
             ejaculate to another person. Male participants should also be advised of the benefit
             for a female partner to use a highly effective method of contraception as condom may
             break or leak

        Exclusion Criteria:

          -  Known active central nervous system (CNS) involvement for dose escalation and specific
             expansion cohorts as determined by the study evaluation team (SET)

          -  Prior solid-organ transplantation

          -  Either of the following: a) Received an autologous stem cell transplant less than or
             equal to (<=)3 months before the first dose of study drug. b) Prior treatment with
             allogenic stem cell transplant <=6 months before the first dose of study drug, has
             evidence of graft versus host disease, or requires immunosuppressant therapy

          -  For participants in the cohort expansions: History of malignancy (other than the
             disease under study in the cohort to which the participant is assigned) within 1 year
             prior to the first administration of study drug. Exceptions are squamous and basal
             cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy which
             in the opinion of the investigator, with concurrence with the sponsor's medical
             monitor, is considered cured with minimal risk of recurrence within 1 year before the
             first dose of study drug. Concomitant malignancies that are unlikely to progress
             and/or preclude evaluation of study endpoints may be allowed after discussion with the
             Study Responsible Physician

          -  Prior treatment with a mucosa-associated lymphoid tissue lymphoma translocation
             protein 1 (MALT1) inhibitor
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Dose-Limiting Toxicity (DLT)
Time Frame:Approximately 21 days
Safety Issue:
Description:The DLTs are based on drug related adverse events and defined as any of the following events: any toxicity that would require discontinuation of treatment; and/or hematological / non-hematological toxicity of Grade 3 or higher.

Secondary Outcome Measures

Measure:JNJ-67856633 Plasma Concentrations
Time Frame:Approximately 2 years
Safety Issue:
Description:Concentration assessment will be done to evaluate the effect of JNJ-67856633.
Measure:Part 1 and Part 2: Change in Gene Expression After Treatment with JNJ-67856633
Time Frame:Approximately 2 years
Safety Issue:
Description:Change in gene expression after treatment with JNJ-67856633 will be analyzed.
Measure:Part 1 and Part 2: Overall Response Rate (ORR)
Time Frame:Approximately 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who have a partial response (PR) and complete response (CR) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.
Measure:Part 1 and Part 2: Complete Response Rate
Time Frame:Approximately 2 years
Safety Issue:
Description:Complete response rate is defined as the percentage of participants who achieve a best response of CR according to the iwCLL, non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.
Measure:Part 1 and Part 2: Time to Response (TTR)
Time Frame:Approximately 2 years
Safety Issue:
Description:TTR is defined for participants who achieved PR or CR as the time from the first dose of study drug to first response of PR or CR.
Measure:Part 1 and Part 2: Duration of Response (DoR)
Time Frame:Approximately 2 years
Safety Issue:
Description:DoR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression or death, whichever comes first.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

January 30, 2020