Home › Trials › NCT06136559

Comparing Nemtabrutinib to Ibrutinib or Acalabrutinib for First Line Treatment of Chronic Lymphocytic Leukemia

A Phase 3, Randomized Study to Compare Nemtabrutinib Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BELLWAVE-011)

PHASE3 · Merck Sharp & Dohme LLC · NCT06136559

This study is testing if a new drug called nemtabrutinib works as well as or better than two existing treatments for people with chronic lymphocytic leukemia who haven’t had treatment before.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment1200 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC (industry)
Drugs / interventionsnemtabrutinib, ibrutinib, acalabrutinib, radiation
Locations196 sites (Mobile, Alabama and 195 other locations)
Trial IDNCT06136559 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of nemtabrutinib compared to the investigator's choice of either ibrutinib or acalabrutinib in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not previously received treatment. The primary goals are to determine if nemtabrutinib is non-inferior to the comparators in terms of objective response rate and if it offers superior progression-free survival. Participants will be monitored for their response to treatment based on established criteria by independent reviewers.

Who should consider this trial

Good fit: Ideal candidates include adults with a confirmed diagnosis of CLL/SLL and active disease requiring treatment.

Not a fit: Patients who have previously received treatment for CLL/SLL may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective first-line treatment option for patients with CLL/SLL.

How similar studies have performed: Other studies have shown promising results with similar treatment approaches, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy.
* Has 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 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.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
* Has gastrointestinal (GI) dysfunction that may affect drug absorption.
* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
* Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
* Has clinically significant cardiovascular disease.
* Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.
* Has history of severe bleeding disorder.
* Has known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Has received any systemic anticancer therapy for CLL/SLL.
* 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.
* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
* Has active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening.
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Where this trial is running

Mobile, Alabama and 195 other locations

+146 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: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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.