Clinical trial NCT04876092: A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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 doses will be escalated in the study and one or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633 will be determined. 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 9 months.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days
measure: Percentage of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 2 years and 9 months
Secondary outcomes:
measure: Plasma Concentration of JNJ-67856633 and Ibrutinib
timeFrame: Up to 2 years and 9 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Lille
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: CHU de Nantes hotel Dieu
city: Paris
country: France
facility: Hopital St Louis
city: Pessac
country: France
facility: CHU de Bordeaux - Hospital Haut-Leveque
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Lund
country: Sweden
facility: Universitetssjukhuset Lund, Onkologiska Kliniken, Lund
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: