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

Primary Purpose

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

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JNJ-67856633
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope
  • University of Nebraska Medical Center
  • Weill Cornell Medicine
  • Icahn School of Medicine at Mount Sinai
  • Memorial Sloan Kettering Cancer Center
  • MD Anderson
  • Monash Medical Centre
  • Peter MacCallum Cancer Centre
  • Linear Clinical Research Ltd
  • Scientia Clinical Research
  • The First Affiliated Hospital of NanChang University
  • Tianjin Medical University Cancer Institute and Hospital
  • Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science
  • The First Affiliated Hospital of Xi'an Jiaotong University
  • Hopital Claude Huriez
  • CHU de Nantes hotel-Dieu
  • Institut Curie
  • Groupe Hospitalier Pitie Salpetriere
  • Centre hospitalier Lyon-Sud
  • Institut Universitaire du Cancer Toulouse - Oncopole
  • CHU Bretonneau
  • Institut Gustave Roussy
  • Universitätsklinikum Münster
  • Universitatsklinikum Ulm
  • Alexandra General Hospital of Athens
  • Hadassah Medical Center
  • Sheba Medical Center
  • Tel Aviv Sourasky Medical Center
  • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
  • ASST Grande Ospedale Metropolitano Niguarda
  • National Cancer Center Hospital
  • Tokai University Hospital
  • National Hospital Organization Nagoya Medical Center
  • Okayama University Hospital
  • The Cancer Institute Hospital of JFCR
  • Seoul National University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Hosp. Univ. Germans Trias I Pujol
  • Hospital de Vall D'Hebron
  • Hosp. Univ. Fund. Jimenez Diaz
  • Hosp. Univ. 12 de Octubre
  • Clinica Univ. de Navarra
  • Hosp. Quiron Madrid Pozuelo
  • Hosp. Clinico Univ. de Salamanca
  • Hosp. Univ. Marques de Valdecilla
  • St Bartholomew's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1 (Dose Escalation): JNJ-67856633

Part 2 (Cohort Expansion): JNJ-67856633

Arm Description

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.

Participants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

JNJ-67856633 Plasma Concentrations
Concentration assessment will be done to evaluate the effect of JNJ-67856633.
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.
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.
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.
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.

Full Information

First Posted
April 2, 2019
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03900598
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
January 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
226 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 (Dose Escalation): JNJ-67856633
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2 (Cohort Expansion): JNJ-67856633
Arm Type
Experimental
Arm Description
Participants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.
Intervention Type
Drug
Intervention Name(s)
JNJ-67856633
Intervention Description
JNJ-67856633 capsule will be administered orally.
Primary Outcome Measure Information:
Title
Part 1: Dose-Limiting Toxicity (DLT)
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.
Time Frame
Approximately 21 days
Title
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Description
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.
Time Frame
Up to 4 years and 11 months
Secondary Outcome Measure Information:
Title
JNJ-67856633 Plasma Concentrations
Description
Concentration assessment will be done to evaluate the effect of JNJ-67856633.
Time Frame
Up to 4 years and 11 months
Title
Part 1 and Part 2: Overall Response Rate (ORR)
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.
Time Frame
Up to 4 years and 11 months
Title
Part 1 and Part 2: Complete Response Rate
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.
Time Frame
Up to 4 years and 11 months
Title
Part 1 and Part 2: Time to Response (TTR)
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.
Time Frame
Up to 4 years and 11 months
Title
Part 1 and Part 2: Duration of Response (DoR)
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.
Time Frame
Up to 4 years and 11 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Facility Name
Monash Medical Centre
City
Clayton
ZIP/Postal Code
3168
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
ZIP/Postal Code
3000
Country
Australia
Facility Name
Linear Clinical Research Ltd
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
Scientia Clinical Research
City
Randwick
ZIP/Postal Code
2031
Country
Australia
Facility Name
The First Affiliated Hospital of NanChang University
City
Nanchang
ZIP/Postal Code
330006
Country
China
Facility Name
Tianjin Medical University Cancer Institute and Hospital
City
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science
City
Tianjin
ZIP/Postal Code
300320
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
Country
China
Facility Name
Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Nantes hotel-Dieu
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Institut Curie
City
PARIS Cedex 5
ZIP/Postal Code
75248
Country
France
Facility Name
Groupe Hospitalier Pitie Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Centre hospitalier Lyon-Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Institut Universitaire du Cancer Toulouse - Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
CHU Bretonneau
City
Tours Cedex 9
ZIP/Postal Code
37044
Country
France
Facility Name
Institut Gustave Roussy
City
VILLEJUIF Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitatsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Alexandra General Hospital of Athens
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
74047
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
National Cancer Center Hospital
City
Chuo-Ku
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Tokai University Hospital
City
Isehara
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
National Hospital Organization Nagoya Medical Center
City
Nagoya-shi
ZIP/Postal Code
460-0001
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
The Cancer Institute Hospital of JFCR
City
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Hosp. Univ. Germans Trias I Pujol
City
Badalona, Barcelona
ZIP/Postal Code
8916
Country
Spain
Facility Name
Hospital de Vall D'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hosp. Univ. 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hosp. Quiron Madrid Pozuelo
City
Pozuelo de Alarcon
ZIP/Postal Code
28223
Country
Spain
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hosp. Univ. Marques de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
St Bartholomew's Hospital
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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