JNJ-67856633 + Ibrutinib for Lymphoma and Leukemia

No longer recruiting at 32 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Disqualifiers: CNS involvement, prior MALT1 inhibitor

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 21

Duration: Up to 2 years and 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The goal is to determine the safety of this combination of JNJ-67856633 (an experimental treatment) and ibrutinib, and to establish the appropriate dose for future studies. Participants will take these drugs orally in cycles, while researchers monitor any side effects. This trial may suit those with NHL or CLL who have not received certain prior treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ibrutinib, one of the drugs being tested, is generally well-tolerated by people with chronic lymphocytic leukemia (CLL). Studies have safely combined ibrutinib with other medications, yielding good results and manageable side effects.

The other drug in the study, JNJ-67856633, has not been extensively studied in humans yet. This trial is in its early stages, focusing on the safety of the drug combination and determining the right dose. During early trials, safety remains the top priority, and researchers closely monitor any side effects. The trial will assess how well participants can tolerate taking both drugs together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about JNJ-67856633 combined with Ibrutinib for treating lymphoma and leukemia because this combination targets cancer cells in a unique way. Ibrutinib is already known for its ability to block the enzyme Bruton's tyrosine kinase (BTK), which is crucial for the survival and growth of cancer cells. JNJ-67856633 adds another layer by potentially enhancing the immune system's ability to fight cancer. This dual approach could offer a more powerful treatment option compared to the current standard therapies, which primarily focus on individual mechanisms. The potential for improved effectiveness and a broader attack on the cancer cells makes this combination promising.

What evidence suggests that JNJ-67856633 and Ibrutinib could be effective for lymphoma and leukemia?

Research has shown that ibrutinib effectively treats chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), particularly in patients with certain high-risk genetic traits. In this trial, participants will receive a combination of JNJ-67856633 with ibrutinib to evaluate whether this combination enhances its tumor-fighting ability. The trial aims to determine the safest and most effective dose of these drugs when used together, as early results suggest potential benefits over using ibrutinib alone. ^{1 2 3 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia. Participants must have available tumor tissue, good organ function, and be in fair health (ECOG grade 0-1). Women who can bear children must use effective contraception and not plan pregnancy or breastfeeding. People are excluded if they've had bad reactions to MALT1 inhibitors before or have active brain involvement by cancer.

Inclusion Criteria

Willing and able to adhere to the lifestyle restrictions specified in this protocol

My heart function is within the normal range.

I am fully active or can carry out light work.

Exclusion Criteria

I had side effects or my disease worsened after treatment with a MALT1 inhibitor.

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JNJ-67856633 and Ibrutinib orally on a 21-day cycle with dose escalation based on dose-limiting toxicities

Up to 2 years and 9 months

21-day cycle visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including radiographic image assessments and adverse events monitoring

Up to 2 years and 9 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• JNJ-67856633

Trial Overview The study is testing the combination of a new drug called JNJ-67856633 with an existing drug named Ibrutinib to find a safe dosage level and see how well it works against certain blood cancers like NHL and CLL. The goal is to establish the recommended dose for further studies.

How Is the Trial Designed?

Group I: JNJ-67856633 and Ibrutinib Experimental Treatment 2 Interventions

Participants will receive JNJ-67856633 together with Ibrutinib orally on a 21-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET).

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Ibrutinib, a Bruton's kinase inhibitor, has shown a high overall response rate of 68% in patients with relapsed or refractory mantle cell lymphoma, with a median progression-free survival of 13.9 months, indicating its efficacy as a treatment option.

In a phase 3 trial for chronic lymphocytic leukemia, ibrutinib demonstrated a significantly higher response rate (43% vs. 4% for ofatumumab) and improved overall survival (90% vs. 81% at 12 months), while being well tolerated with no dose-limiting toxicity, making it a suitable option for older patients and those not eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib. Lee, CS., Rattu, MA., Kim, SS.[2021]

Ibrutinib (Imbruvica) is an effective treatment for chronic lymphocytic leukemia, targeting specific pathways to inhibit cancer cell growth.

Tasimelteon (Hetlioz) is beneficial for individuals with non-24-hour sleep-wake disorder, helping to regulate sleep patterns, while anti-inhibitor coagulant complex (Feiba) is used to prevent or reduce bleeding episodes in patients with hemophilia A or B, demonstrating its efficacy in managing bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

Citations

1. withpower.com withpower.com/trial/phase-1-leukemia-6-2021-eaf46

JNJ-67856633 + Ibrutinib for Lymphoma and Leukemia This trial is testing two drugs, JNJ-67856633 and ibrutinib, to find the safest and most effective dose for treating certain blood cancers.

2. jnj.com jnj.com/innovativemedicine/emea/imbruvicarvibrutinib-combination-therapy-data-two-studies-and-long-term-integrated-analysis

Imbruvica®▼(ibrutinib) Combination Therapy Data ... Imbruvica®▽(ibrutinib) Combination Therapy Data From Two Studies and Long-Term Integrated Analysis Presented at ASH 2019 Show Efficacy and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40353821/

Real-world survival outcomes in first-line ibrutinib-treated ... In patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), high-risk cytogenetic features such as del(17p), del(11q), ...

4. veri.larvol.com veri.larvol.com/news/jnj-64264681/drug

News - JNJ-4681 Taken together, the in vitro and in vivo data for JNJ‑67856633 and JNJ-64264681 suggest that combination therapy can increase the anti-tumor effect of the ...

5. jnj.com jnj.com/media-center/press-releases/imbruvica-ibrutinib-combination-therapy-data-from-two-studies-and-long-term-integrated-analysis-presented-at-ash-2019-show-efficacy-and-safety-in-first-line-treatment-of-chronic-lymphocytic-leukemia

IMBRUVICA® (ibrutinib) Combination Therapy Data From ... IMBRUVICA in combination with rituximab versus fludarabine, cyclophosphamide and rituximab showed statistically significant difference in progression-free ...

6. ctv.veeva.com ctv.veeva.com/study/a-study-of-the-malt1-inhibitor-jnj-67856633-and-ibrutinib-in-combination-in-b-cell-nhl-and-cll

A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in ... 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 ...