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Comparing two treatments for relapsed chronic lymphocytic leukemia

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)

PHASE3 · Merck Sharp & Dohme LLC · NCT05947851

This study is testing if a new combination of two drugs, nemtabrutinib and venetoclax, can help people with relapsed chronic lymphocytic leukemia live longer without their cancer getting worse compared to the usual treatment.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment735 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC (industry)
Drugs / interventionsRituximab, Nemtabrutinib, radiation
Locations54 sites (Springdale, Arkansas and 53 other locations)
Trial IDNCT05947851 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of nemtabrutinib combined with venetoclax compared to the standard treatment of venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The primary goal is to determine if the new combination improves progression-free survival as assessed by independent reviewers. Participants must have a confirmed diagnosis and meet specific health criteria to be eligible for the trial.

Who should consider this trial

Good fit: Ideal candidates are individuals with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have previously received at least one therapy.

Not a fit: Patients who are not relapsed or refractory or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a more effective option for patients with relapsed chronic lymphocytic leukemia.

How similar studies have performed: Other studies have shown promising results with similar treatment combinations in chronic lymphocytic leukemia, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy
* Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, and immunoglobulin heavy chain gene (IGHV) mutation status results required before randomization for Part 2 participants only
* Relapsed or refractory to at least 1 prior available therapy
* Have at least 1 marker of disease burden
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization
* Has a life expectancy of at least 3 months
* Has the ability to swallow and retain oral medication
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening
* Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria
* Participants with adequate organ function with specimens collected within 7 days before the start of study intervention
* If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception
* Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding

Exclusion Criteria:

* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection
* Has gastrointestinal (GI) dysfunction that may affect drug absorption
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL
* Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening
* Clinically significant cardiovascular disease
* Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients
* Has history of severe bleeding disorders (eg, hemophilia)
* Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization
* Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) within ≤ 12 months before randomization or has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids
* Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
* Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications

Where this trial is running

Springdale, Arkansas and 53 other locations

+4 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic, Small-Cell Lymphoma, Lymphoma, Small Lymphocytic, CLL, SLL

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.