A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
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)
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Chronic Lymphocytic
- Small-Cell Lymphoma
- Lymphoma, Small Lymphocytic
- CLL
- SLL
At a glance
- Phase
- Phase 3
- Study type
- Interventional
- Sponsor
- Merck Sharp & Dohme LLC
- Enrolment target
- 735
- Started
- 8 August 2023
- Main results due
- 1 June 2032
- Study sites
- 79
- Registry updated
- 24 September 2026
Can you take part?
- Aged 18 years and over.
- Open to any sex.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the full eligibility 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
What this study is about
In the sponsor’s own words, from the registry.
The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).
Study sites(79)
Highlands Oncology Group ( Site 5405)
Springdale, Arkansas, United States
Recruiting
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Long Beach, California, United States
Recruiting
Clermont Oncology Center ( Site 5430)
Clermont, Florida, United States
Recruiting
Memorial Hospital West ( Site 5410)
Pembroke Pines, Florida, United States
Recruiting
Fort Wayne Medical Oncology and Hematology ( Site 5444)
Fort Wayne, Indiana, United States
Recruiting
Center for Cancer and Blood Disorders ( Site 5439)
Bethesda, Maryland, United States
Recruiting
Hattiesburg Clinic Hematology/Oncology ( Site 5416)
Hattiesburg, Mississippi, United States
Recruiting
MidAmerica Cancer Care, LLC ( Site 5426)
Kansas City, Missouri, United States
Recruiting
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433)
Billings, Montana, United States
Recruiting
Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434)
Reno, Nevada, United States
Recruiting
New York Oncology Hematology, P.C. ( Site 5453)
Albany, New York, United States
Recruiting
Oregon Health and Science University ( Site 5425)
Portland, Oregon, United States
Recruiting
Avera Cancer Institute- Research ( Site 5437)
Sioux Falls, South Dakota, United States
Recruiting
PatientCare Clinical Research LLC ( Site 5435)
Sugar Land, Texas, United States
Recruiting
University of Virginia Cancer Center ( Site 5402)
Charlottesville, Virginia, United States
Recruiting
Vista Oncology ( Site 5449)
Olympia, Washington, United States
Recruiting
Medical Oncology Associates, PS ( Site 5406)
Spokane, Washington, United States
Recruiting
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Madison, Wisconsin, United States
Completed
Instituto Alexander Fleming ( Site 1005)
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Recruiting
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)
Mar del Plata, Buenos Aires, Argentina
Recruiting
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002)
Buenos Aires, Buenos Aires F.D., Argentina
Recruiting
Sanatorio Parque ( Site 1003)
Rosario, Santa Fe Province, Argentina
Recruiting
Centro Medico Fleischer ( Site 1006)
Buenos Aires, Argentina
Recruiting
Hospital Aleman-oncohematologic diseases ( Site 1001)
Buenos Aires, Argentina
Recruiting
Royal Adelaide Hospital ( Site 1104)
Adelaide, South Australia, Australia
Recruiting
Box Hill Hospital ( Site 1106)
Box Hill, Victoria, Australia
Recruiting
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)
Melbourne, Victoria, Australia
Recruiting
UZ Leuven-Hematology ( Site 1200)
Leuven, Vlaams-Brabant, Belgium
Recruiting
ZAS Cadix ( Site 1203)
Antwerp, Belgium
Recruiting
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
São Paulo, Brazil
Active, not recruiting
The Moncton Hospital ( Site 1414)
Moncton, New Brunswick, Canada
Recruiting
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)
Greenfield Park, Quebec, Canada
Recruiting
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)
Sherbrooke, Quebec, Canada
Recruiting
Biocenter ( Site 1507)
Concepción, Biobio, Chile
Recruiting
IC La Serena Research ( Site 1506)
La Serena, Coquimbo Region, Chile
Recruiting
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
Santiago, Region M. de Santiago, Chile
Recruiting
FALP-UIDO ( Site 1500)
Santiago, Region M. de Santiago, Chile
Recruiting
Clínica Inmunocel ( Site 1511)
Santiago, Region M. de Santiago, Chile
Recruiting
Fundación Valle del Lili ( Site 1703)
Cali, Valle del Cauca Department, Colombia
Recruiting
Hopital Claude Huriez - CHU de Lille ( Site 2107)
Lille, Nord, France
Recruiting
Centre Hospitalier Universitaire Estaing ( Site 2105)
Clermont-Ferrand, Puy-de-Dome, France
Recruiting
CHD Vendee ( Site 2100)
La Roche-sur-Yon, Vendee, France
Recruiting
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)
Trier, Rhineland-Palatinate, Germany
Recruiting
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)
Leipzig, Saxony, Germany
Recruiting
Evangelismos General Hospital of Athens ( Site 2302)
Athens, Attica, Greece
Recruiting
General Hospital of Athens "Laiko" ( Site 2308)
Athens, Attica, Greece
Recruiting
General Hospital of Athens "Laiko" ( Site 2309)
Athens, Attica, Greece
Recruiting
Rambam Health Care Campus ( Site 2801)
Haifa, Israel
Recruiting
Hadassah Medical Center-Hemato-Oncology ( Site 2812)
Jerusalem, Israel
Recruiting
Sheba Medical Center-Hemato Oncology ( Site 2809)
Ramat Gan, Israel
Recruiting
Sourasky Medical Center ( Site 2811)
Tel Aviv, Israel
Recruiting
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)
Alessandria, Italy
Recruiting
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)
Milan, Italy
Recruiting
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)
Reggio Emilia, Italy
Recruiting
National Hospital Organization Osaka National Hospital ( Site 3004)
Osaka, Japan
Recruiting
Centro de Infusion Superare ( Site 3314)
Mexico City, Mexico City, Mexico
Recruiting
Health Pharma Professional Research S.A. de C.V: ( Site 3301)
Mexico City, Mexico City, Mexico
Recruiting
Centro de Investigacion Clinica Chapultepec ( Site 3309)
Morelia, Michoacán, Mexico
Recruiting
Christchurch Hospital ( Site 3503)
Christchurch, Canterbury, New Zealand
Recruiting
Palmerston North Hospital ( Site 3506)
Palmerston North, Manawatu-Wanganui, New Zealand
Recruiting
Showing 60 of 79 sites — filter to narrow it down. 76 of the 79 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT05947851. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
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