Nemtabrutinib + Venetoclax for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

+59 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: BCL2 inhibitors, BTK inhibitors

Disqualifiers: Active infection, CNS involvement, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are currently being treated with certain medications like p-glycoprotein substrates, CYP3A inducers, or inhibitors. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

What data supports the effectiveness of the drug combination Nemtabrutinib + Venetoclax for Chronic Lymphocytic Leukemia?

Research shows that venetoclax, when used with rituximab, is effective in treating chronic lymphocytic leukemia, providing long-lasting responses and manageable side effects. This combination has been more effective than other treatments in prolonging the time patients live without the disease getting worse. ^{1 2 3 4 5}

Is the combination of Nemtabrutinib and Venetoclax safe for treating chronic lymphocytic leukemia?

Venetoclax, often used with rituximab, has shown an acceptable safety profile in treating chronic lymphocytic leukemia, with manageable side effects like neutropenia (low white blood cell count) and gastrointestinal issues. While specific safety data for Nemtabrutinib is not provided, the combination of venetoclax with other drugs has been generally safe in clinical trials. ^{1 2 5 6 7}

What makes the drug combination of Nemtabrutinib, Rituximab, and Venetoclax unique for treating chronic lymphocytic leukemia?

This drug combination is unique because it includes Nemtabrutinib, which is not commonly used in standard treatments for chronic lymphocytic leukemia. Venetoclax, a BCL-2 inhibitor, is already known for its effectiveness in combination with Rituximab, but the addition of Nemtabrutinib could offer a novel approach by potentially enhancing the treatment's efficacy or safety profile. ^{1 2 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

Inclusion Criteria

I have been diagnosed with CLL/SLL and need treatment.

My organ function is good, tested within the last week.

I am HBsAg positive but have been on HBV therapy for 4 weeks with undetectable HBV DNA.

Exclusion Criteria

Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study

I am still recovering from major surgery or have complications.

I am HIV-positive with a history of specific conditions or infections in the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nemtabrutinib plus venetoclax or venetoclax plus rituximab for up to 2 years or until progressive disease

Up to 2 years

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 71 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Nemtabrutinib (Other)
• Rituximab (Monoclonal Antibodies)
• Venetoclax (Other)

Trial Overview 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.

Participant Groups

Group I: Nemtabrutinib + Venetoclax Experimental Treatment 2 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 + Rituximab Active Control 2 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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402) Greenfield Park, Canada

Oregon Health and Science University ( Site 5425) Portland, OR

Highlands Oncology Group ( Site 5405) Springdale, AR

University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423) Madison, WI

More Trial Locations

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Three new oral small molecule inhibitors—ibrutinib, idelalisib, and venetoclax—have been approved for chronic lymphocytic leukemia (CLL) treatment in the last four years, showing excellent efficacy.

These inhibitors have different toxicity profiles, which is important for tailoring treatment, especially in older patients, and raises questions about how to best sequence their use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The Conundrum of Many Options. Jain, N., Thompson, P., Ferrajoli, A., et al.[2020]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The Conundrum of Many Options. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for venetoclax. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Protocol description of the HOVON 141/VISION trial: a prospective, multicentre, randomised phase II trial of ibrutinib plus venetoclax in patients with creatinine clearance ≥30 mL/min who have relapsed or refractory chronic lymphocytic leukaemia (RR-CLL) with or without TP53 aberrations. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]