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

Lymphoma, Non-Hodgkin Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03900598
• Other study ID #: CR108587
• Secondary ID: 2018-003549-4067
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 3, 2019
• Est. completion date: January 30, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 226
• Est. completion date: January 30, 2026
• Est. primary completion date: December 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-67856633
JNJ-67856633 capsule will be administered orally.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	Linear Clinical Research Ltd	Nedlands
Australia	Scientia Clinical Research	Randwick
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	The First Affiliated Hospital of Xian Jiaotong University	Xi'an
France	Hopital Claude Huriez	Lille
France	CHU de Nantes hotel Dieu	Nantes Cedex 1
France	Groupe Hospitalier Pitie Salpetriere	Paris
France	Institut Curie	PARIS Cedex 5
France	Centre hospitalier Lyon-Sud	Pierre Benite
France	Institut Universitaire du Cancer Toulouse - Oncopole	Toulouse
France	CHU Bretonneau	Tours Cedex 9
France	Institut Gustave Roussy	VILLEJUIF Cedex
Germany	Universitatsklinikum Munster	Münster
Germany	Universitatsklinikum Ulm	Ulm
Greece	Alexandra General Hospital of Athens	Athens
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Japan	National Cancer Center Hospital	Chuo Ku
Japan	Tokai University Hospital	Isehara
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Okayama University Hospital	Okayama
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona, Barcelona
Spain	Hospital de Vall D'Hebron	Barcelona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon
Spain	Hosp Clinico Univ de Salamanca	Salamanca
Spain	Hosp. Univ. Marques de Valdecilla	Santander
United Kingdom	St Bartholomew's Hospital	London
United States	City of Hope	Duarte	California
United States	MD Anderson	Houston	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  China,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Dose-Limiting Toxicity (DLT)	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.	Approximately 21 days
Primary	Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 4 years and 11 months
Secondary	JNJ-67856633 Plasma Concentrations	Concentration assessment will be done to evaluate the effect of JNJ-67856633.	Up to 4 years and 11 months
Secondary	Part 1 and Part 2: Overall Response Rate (ORR)	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.	Up to 4 years and 11 months
Secondary	Part 1 and Part 2: Complete Response Rate	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.	Up to 4 years and 11 months
Secondary	Part 1 and Part 2: Time to Response (TTR)	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.	Up to 4 years and 11 months
Secondary	Part 1 and Part 2: Duration of Response (DoR)	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.	Up to 4 years and 11 months