Lymphoma, Non-HodgkinPhase 1NCT04657224
A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
A Phase 1 study testing JNJ-64264681 and JNJ-67856633 in people with Lymphoma, Non-Hodgkin and Chronic Lymphocytic Leukemia, run by Janssen Research & Development, LLC at 28 sites in 12 countries.
Trial summary
The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Non-Hodgkin, Chronic Lymphocytic Leukemia
- What is being tested?
- JNJ-64264681 and JNJ-67856633
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 28 sitesin 12 countries
- Study dates
- 25 Feb 2021to 16 Jan 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds
- Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available at baseline as described in the protocol. This is not required for participants with chronic lymphocytic leukemia (CLL)
- Women of childbearing potential must agree to use a barrier method of contraception; use a highly effective preferably user-independent method of contraception; not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; not to plan to become pregnant; and not to breast-feed
Who cannot join
- Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK) or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without evidence of progression or intolerable class-related toxicity will be eligible
- Known (active) central nervous system (CNS) involvement
- Received prior solid organ transplantation
- Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients
- Toxicities from previous anti-cancer therapies that have not resolved to baseline levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade 2] and peripheral neuropathy [Grade 1])
Trial locations and contacts
28 sites in 12 countries.
28 sites in 12 countries
Australia4 sites
Monash Medical Centre
Clayton, 3168
Peter MacCallum Cancer Centre
Melbourne, 3000
Linear Clinical Research Ltd
Nedlands, 6009
Scientia Clinical Research
Randwick, 2031
France4 sites
CHRU de Lille Hopital Claude Huriez
Lille, 59037
Chu Hotel Dieu
Nantes, 44093
Centre hospitalier Lyon-Sud
Pierre-Bénite, 69495
CHU Bretonneau
Tours, 37044
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 214
Pratia Onkologia Katowice
Katowice, 40 519
Pratia MCM Krakow
Krakow, 30-727
Centrum Medyczne Pratia Poznan
Skorzewo, 60 185
Belgium3 sites
AZ St.-Jan Brugge-Oostende AV
Bruges, 8000
Universitair Ziekenhuis Gent - UZ GENT
Ghent, 9000
CHU UCL Namur - Site Godinne
Yvoir, 5530
Israel3 sites
Hadassah Medical Center
Jerusalem, 9112001
Sheba Medical Center
Ramat Gan, 52621
Tel Aviv Sourasky MC
Tel Aviv, 6423906
South Korea3 sites
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Seoul National University Hospital
Seoul, 3080
Spain2 sites
Hosp Univ Vall D Hebron
Barcelona, 08035
Hosp Univ Fund Jimenez Diaz
Madrid, 28040
United States1 site
Stony Brook University Medical Center
Stony Brook, New York, 11794
Ukraine1 site
Medical Center of Limited Liability Company Arensia Exploratory Medicine
Kyiv, 01135
About this study
Official title: A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).
Read the detailed description
Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than 60 subtypes have been identified and classified by the world health organization. JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28 days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal of consent, death, 6 months after start of first subsequent antineoplastic therapy, after the clinical cut off (CCO) date participants will be withdrawn from the study 30 days after the last dose of study drugs were administered). The total study duration is estimated at 2 years and 2 months. Safety assessments will include physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, eastern cooperative oncology group performance status, echocardiogram, and adverse events monitoring.
- Being tested
- JNJ-64264681, JNJ-67856633
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-64264681Drug
JNJ-64264681 capsules will be administered orally.
JNJ-67856633Drug
JNJ-67856633 capsules or tablets will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 | Experimental | Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator. Receives: Drug: JNJ-64264681; Drug: JNJ-67856633 |
| Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 | Experimental | Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. Receives: Drug: JNJ-64264681; Drug: JNJ-67856633 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Number of Participants with Dose-limiting Toxicity (DLT)
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Measured: Up to 28 days
Part A and Part B: 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.
Measured: Up to 3 years and 9 months
Secondary outcomes (5)
Plasma Concentrations of JNJ-64264681 and JNJ-67856633
Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed.
Measured: Up to 3 years and 9 months
Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)
BTK occupancy will be assessed.
Measured: Up to 3 years and 9 months
Overall Response Rate (ORR)
ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM).
Measured: Up to 3 years and 9 months
Time to First Response
Time to first response defined for the responders as the time from the date of first dose of study treatment to the date of initial documentation of a first response as defined in the disease-specific response criteria.
Measured: Up to 3 years and 9 months
Duration of Response
DOR will be calculated from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.
Measured: Up to 3 years and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start25 Feb 2021
- Primary completion16 Jan 2025
- Study completion16 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma, Non-HodgkinStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trials, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04657224
- Sponsor's protocol ID
- CR108877
- Other IDs
- 64264681LYM1002, 2020-003149-12, 2024-512687-66-00
- Status last verified
- Aug 2025
- First submitted
- 1 Dec 2020
- Last updated
- 21 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT04657224
- Acronym / sponsor ID
- CR108877
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 16 Jan 2025 (actual)
- Study completion
- 16 Jan 2025 (actual)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).
Detailed description
Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than 60 subtypes have been identified and classified by the world health organization. JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28 days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal of consent, death, 6 months after start of first subsequent antineoplastic therapy, after the clinical cut off (CCO) date participants will be withdrawn from the study 30 days after the last dose of study drugs were administered). The total study duration is estimated at 2 years and 2 months. Safety assessments will include physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, eastern cooperative oncology group performance status, echocardiogram, and adverse events monitoring.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 | Experimental | Drug: JNJ-64264681, Drug: JNJ-67856633Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator. |
| Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 | Experimental | Drug: JNJ-64264681, Drug: JNJ-67856633Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds
- Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available at baseline as described in the protocol. This is not required for participants with chronic lymphocytic leukemia (CLL)
- Women of childbearing potential must agree to use a barrier method of contraception; use a highly effective preferably user-independent method of contraception; not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; not to plan to become pregnant; and not to breast-feed
Key exclusion criteria (5 listed)
- Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK) or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without evidence of progression or intolerable class-related toxicity will be eligible
- Known (active) central nervous system (CNS) involvement
- Received prior solid organ transplantation
- Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients
- Toxicities from previous anti-cancer therapies that have not resolved to baseline levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade 2] and peripheral neuropathy [Grade 1])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-64264681JNJ-64264681 capsules will be administered orally. | Drug | Part A: Dose escalation: JNJ-64264681 and JNJ-67856633, Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 |
| JNJ-67856633JNJ-67856633 capsules or tablets will be administered orally. | Drug | Part A: Dose escalation: JNJ-64264681 and JNJ-67856633, Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 |
Primary outcome
Part A: Number of Participants with Dose-limiting Toxicity (DLT)
Time frame: Up to 28 days
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time frame: Up to 3 years and 9 months
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.
5 secondary outcomes
Plasma Concentrations of JNJ-64264681 and JNJ-67856633
Time frame: Up to 3 years and 9 months
Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)
Time frame: Up to 3 years and 9 months
Overall Response Rate (ORR)
Time frame: Up to 3 years and 9 months
Time to First Response
Time frame: Up to 3 years and 9 months
Duration of Response
Time frame: Up to 3 years and 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trials study director
Janssen Research & Development, LLC
28 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JNJ-64264681 and JNJ-67856633 in people with Lymphoma, Non-Hodgkin and Chronic Lymphocytic Leukemia, run by Janssen Research & Development, LLC at 28 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Australia, France, Poland, Belgium, Israel and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Number of Participants with Dose-limiting Toxicity (DLT) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025.