What side effects are associated with this type of intervention?

Common side effects of BTK inhibitors like ibrutinib include bleeding, atrial fibrillation, hypertension, and infections. Patients may also experience diarrhea and neutropenia. For BCL-2 inhibitors like venetoclax, common side effects include neutropenia, infections, and tumor lysis syndrome. Both classes of drugs can have significant impacts on blood cell counts and may require careful monitoring and dose adjustments.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic B-Cell Leukemia, particularly focusing on BTK inhibitors and BCL-2 inhibitors. Ibrutinib, a first-generation BTK inhibitor, was one of the first in its class to receive approval for CLL. Acalabrutinib and Zanubrutinib, second-generation BTK inhibitors, have also been approved due to their improved tolerability and efficacy. Venetoclax, a BCL-2 inhibitor, has been approved for use in CLL, often in combination with other agents like rituximab or obinutuzumab, to enhance treatment efficacy and achieve deeper remissions. These approvals highlight the evolving landscape of targeted therapies in CLL treatment.

What other types of research exist?

Promising novel alternatives for CLL treatment in 2024 include: 1) Ibrutinib (a BTK inhibitor) combined with Obinutuzumab (an anti-CD20 monoclonal antibody), which has shown improved progression-free survival (PFS) in clinical trials. 2) Acalabrutinib (another BTK inhibitor) as monotherapy or in combination with Venetoclax. 3) CAR-T cell therapy, particularly for patients with refractory or relapsed CLL. These alternatives offer targeted approaches and have demonstrated efficacy in clinical studies.

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Nemtabrutinib + Venetoclax for Chronic Lymphocytic Leukemia

Phase 3

Recruiting

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 108 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests a new drug (nemtabrutinib) with an existing one (venetoclax) in patients with CLL or SLL who haven't responded to other treatments. The drugs work together to stop cancer growth and kill cancer cells. Venetoclax is a selective Bcl-2 inhibitor approved for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Who is the study for?

This trial is for people with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma who have tried at least one therapy before. They must be able to take oral meds, not be pregnant or breastfeeding, and use effective contraception if necessary. They should have a life expectancy of over 3 months and good organ function.

What is being tested?

The study tests the combination of Nemtabrutinib plus Venetoclax against Venetoclax with Rituximab in treating CLL/SLL. It aims to see if the new combo improves how long patients live without their disease getting worse compared to the existing treatment option.

What are the potential side effects?

Possible side effects include reactions related to infusion, fatigue, digestive issues that might affect drug absorption, blood disorders including severe bleeding problems, increased risk of infections due to hepatitis B or C virus reactivation, and potential interactions with other drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 108 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 108 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 108 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

Part 1: Number of participants discontinuing study treatment due to AEs

Part 1: Number of participants experiencing adverse events (AEs)

Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)

+1 more

Secondary study objectives

Part 2: Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR

Part 2: Number of participants discontinuing study treatment due to AEs

Part 2: Number of participants experiencing AEs

+3 more

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Nemtabrutinib + VenetoclaxExperimental Treatment2 Interventions

Participants will receive nemtrabrutinib oral tablets at specified doses daily starting at Cycle 1 Day 1 (C1D1) and venetoclax oral tablets at doses of 20 mg up to 400 mg daily starting at Cycle 2 Day 1 (C2D1) up to 2 years post C2D1 or until progressive disease (PD) or discontinuation. A cycle = 4 weeks.

Group II: Venetoclax + RituximabActive Control2 Interventions

Participants will receive venetoclax oral tablets at doses from 20 mg up to 400 mg daily starting at C1D1 on 4-week cycles up to 2 years and rituximab or biosimilar at 375 mg/m\^2 up to 500 mg/m2 intravenous infusion once per 28-day cycle starting at C2D1, for 6 total cycles. Treatment will continue until progressive disease (PD) or discontinuation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nemtabrutinib

2023

Completed Phase 1

~100

Venetoclax

2019

Completed Phase 3

~2240

Do I qualify?Apply below to find out

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

BTK inhibitors, such as Nemtabrutinib, work by blocking Bruton's tyrosine kinase, a crucial enzyme in the B-cell receptor signaling pathway. This inhibition disrupts the survival and proliferation of malignant B-cells. BCL-2 inhibitors, like Venetoclax, target the B-cell lymphoma 2 protein, which prevents apoptosis (programmed cell death) in cancer cells. By inhibiting BCL-2, Venetoclax promotes the death of these malignant cells. These mechanisms are vital for Chronic B-Cell Leukemia patients as they directly target the pathways that allow cancer cells to survive and proliferate, offering a more effective and targeted approach to treatment.