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.
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
Drug | Synonyms | Arms |
---|
JNJ-67856633 | | Part 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. A prescreening period may also apply to participants in
select cohorts in Part 2. The total study duration will be approximately 4 years and 11
months. 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
Name | Type | Description | Interventions |
---|
Part 1 (Dose Escalation): JNJ-67856633 | Experimental | Participants 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. | |
Part 2 (Cohort Expansion): JNJ-67856633 | Experimental | Participants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. | |
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 graft
versus host disease within the last 4 weeks
- 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: | Up to 4 years and 11 months |
Safety Issue: | |
Description: | Concentration assessment will be done to evaluate the effect of JNJ-67856633. |
Measure: | Part 1 and Part 2: Overall Response Rate (ORR) |
Time Frame: | Up to 4 years and 11 months |
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: | Up to 4 years and 11 months |
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: | Up to 4 years and 11 months |
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: | Up to 4 years and 11 months |
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
August 13, 2021