Clinical trial NCT03900598: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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.

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

Primary outcomes:
measure: Part 1: Dose-Limiting Toxicity (DLT)
timeFrame: Approximately 21 days
measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 4 years and 11 months
Secondary outcomes:
measure: JNJ-67856633 Plasma Concentrations
timeFrame: Up to 4 years and 11 months
measure: Part 1 and Part 2: Overall Response Rate (ORR)
timeFrame: Up to 4 years and 11 months
measure: Part 1 and Part 2: Complete Response Rate
timeFrame: Up to 4 years and 11 months
measure: Part 1 and Part 2: Time to Response (TTR)
timeFrame: Up to 4 years and 11 months
measure: Part 1 and Part 2: Duration of Response (DoR)
timeFrame: Up to 4 years and 11 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
city: Randwick
country: Australia
facility: Scientia Clinical Research
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Tianjin
country: China
facility: Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Lille
country: France
facility: Hopital Claude Huriez
city: Nantes Cedex 1
country: France
facility: CHU de Nantes hotel Dieu
city: PARIS Cedex 5
country: France
facility: Institut Curie
city: Paris
country: France
facility: Groupe Hospitalier Pitie Salpetriere
city: Pierre Benite
country: France
facility: Centre hospitalier Lyon-Sud
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole
city: Tours Cedex 9
country: France
facility: CHU Bretonneau
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave Roussy
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Isehara
country: Japan
facility: Tokai University Hospital
city: Nagoya-shi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital de Vall D'Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: