What is the mechanism of action of this treatment?

The most common treatments for Non-Hodgkin's Lymphoma (NHL) often involve targeting B cell pathways, such as with Bruton tyrosine kinase (BTK) inhibitors like ibrutinib. BTK inhibitors block the BTK enzyme, essential for B cell receptor signaling, thereby disrupting the survival and proliferation of malignant B cells. Additionally, agents like JNJ-67856633 likely target other components of the B cell signaling pathways, further impairing the growth and survival of lymphoma cells. This targeted approach is crucial for NHL patients as it offers the potential for more effective and less toxic treatments compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common side effects of BTK inhibitors like Ibrutinib, used in the treatment of Non-Hodgkin's Lymphoma, include increased risk of bleeding, infections, and cardiovascular issues such as atrial fibrillation. Patients may also experience gastrointestinal symptoms like diarrhea, nausea, and vomiting. Additionally, fatigue, musculoskeletal pain, and rash are frequently reported. For agents targeting B cell pathways, similar side effects may occur, with added risks of immunosuppression and potential liver function abnormalities.

What prior FDA approvals exist?

Ibrutinib, a BTK inhibitor, has been FDA-approved for the treatment of various B cell malignancies, including Non-Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Other BTK inhibitors like acalabrutinib and zanubrutinib have also received FDA approval for similar indications. Additionally, monoclonal antibodies targeting B cell pathways, such as rituximab and obinutuzumab, have been approved for NHL treatment. These therapies focus on disrupting B cell receptor signaling and inducing apoptosis in malignant B cells.

What other types of research exist?

Promising novel alternatives for NHL treatment in 2024 include: 1) Acalabrutinib, a next-generation BTK inhibitor with a favorable safety profile. 2) Venetoclax, a BCL2 inhibitor that has shown efficacy in combination with other agents. 3) CAR-T cell therapies, such as axicabtagene ciloleucel and tisagenlecleucel, which have demonstrated significant efficacy in relapsed/refractory NHL. 4) Bispecific antibodies like mosunetuzumab, targeting CD20 and CD3, offering a novel mechanism of action.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

JNJ-67856633 + Ibrutinib for Lymphoma and Leukemia

Phase 1

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cardiac parameters within the specified range

Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Must not have

Prior treatment with JNJ-67856633 or another MALT1 inhibitor that is associated with disease progression or intolerable toxicities

Known (active) Central Nervous System (CNS) involvement

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years and 9 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, JNJ-67856633 and ibrutinib, to find the safest and most effective dose for treating certain blood cancers. It targets patients with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), who may not respond well to standard treatments. These drugs work by blocking proteins that help cancer cells grow.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical reactions seen with cancer treatments such as nausea, fatigue, diarrhea, risk of infection due to low blood cell counts, liver problems indicated by abnormal tests, and possibly heart issues which will be closely monitored.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My heart function is within the normal range.

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I am fully active or can carry out light work.

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I have available tumor tissue for testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My cancer has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years and 9 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years and 9 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years and 9 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants with Adverse Events (AEs) by Severity

Percentage of Participants with Dose-Limiting Toxicity (DLT)

Secondary study objectives

Plasma Concentration of JNJ-67856633 and Ibrutinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: JNJ-67856633 and IbrutinibExperimental Treatment2 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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) often involve targeting B cell pathways, such as with Bruton tyrosine kinase (BTK) inhibitors like ibrutinib. BTK inhibitors block the BTK enzyme, essential for B cell receptor signaling, thereby disrupting the survival and proliferation of malignant B cells. Additionally, agents like JNJ-67856633 likely target other components of the B cell signaling pathways, further impairing the growth and survival of lymphoma cells. This targeted approach is crucial for NHL patients as it offers the potential for more effective and less toxic treatments compared to traditional chemotherapy.

Response to second-line therapy defines the potential for cure in patients with recurrent diffuse large B-cell lymphoma: implications for the development of novel therapeutic strategies.