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).
NCT ID: NCT05947851
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
735 participants
INTERVENTIONAL
2023-08-08
2035-07-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Nemtabrutinib + Venetoclax
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.
Nemtabrutinib
5, 20, 45, and 65 mg tablets
Venetoclax
10, 50, and 100 mg tablets
Venetoclax + Rituximab
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.
Venetoclax
10, 50, and 100 mg tablets
Rituximab
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Interventions
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Nemtabrutinib
5, 20, 45, and 65 mg tablets
Venetoclax
10, 50, and 100 mg tablets
Rituximab
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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Highlands Oncology Group ( Site 5405)
Springdale, Arkansas, United States
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Long Beach, California, United States
Memorial Hospital West ( Site 5410)
Pembroke Pines, Florida, United States
Oregon Health and Science University ( Site 5425)
Portland, Oregon, United States
Medical Oncology Associates, PS ( Site 5406)
Spokane, Washington, United States
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Madison, Wisconsin, United States
Instituto Alexander Fleming ( Site 1005)
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)
Mar del Plata, Buenos Aires, Argentina
Sanatorio Parque ( Site 1003)
Rosario, Santa Fe Province, Argentina
Centro Medico Fleischer ( Site 1006)
Buenos Aires, , Argentina
Hospital Aleman-oncohematologic diseases ( Site 1001)
Buenos Aires, , Argentina
Royal Adelaide Hospital ( Site 1104)
Adelaide, South Australia, Australia
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)
Melbourne, Victoria, Australia
UZ Leuven-Hematology ( Site 1200)
Leuven, Vlaams-Brabant, Belgium
ZAS Cadix ( Site 1203)
Antwerp, , Belgium
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
São Paulo, , Brazil
The Moncton Hospital ( Site 1414)
Moncton, New Brunswick, Canada
IC La Serena Research ( Site 1506)
La Serena, Coquimbo Region, Chile
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
Santiago, Region M. de Santiago, Chile
FALP-UIDO ( Site 1500)
Santiago, Region M. de Santiago, Chile
Clínica Inmunocel ( Site 1511)
Santiago, Region M. de Santiago, Chile
Biocenter ( Site 1507)
Concepción, Región del Biobío, Chile
Fundación Valle del Lili ( Site 1703)
Cali, Valle del Cauca Department, Colombia
Hopital Claude Huriez - CHU de Lille ( Site 2107)
Lille, Nord, France
Centre Hospitalier Universitaire Estaing ( Site 2105)
Clermont-Ferrand, Puy-de-Dome, France
CHD Vendee ( Site 2100)
La Roche-sur-Yon, Vendee, France
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)
Trier, Rhineland-Palatinate, Germany
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)
Leipzig, Saxony, Germany
Rambam Health Care Campus ( Site 2801)
Haifa, , Israel
Hadassah Medical Center-Hemato-Oncology ( Site 2812)
Jerusalem, , Israel
Sheba Medical Center-Hemato Oncology ( Site 2809)
Ramat Gan, , Israel
Sourasky Medical Center ( Site 2811)
Tel Aviv, , Israel
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)
Alessandria, Ancona, Italy
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)
Milan, , Italy
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)
Reggio Emilia, , Italy
Centro de Infusion Superare ( Site 3314)
Mexico City, Mexico City, Mexico
Health Pharma Professional Research S.A. de C.V: ( Site 3301)
Mexico City, Mexico City, Mexico
Centro de Investigacion Clinica Chapultepec ( Site 3309)
Morelia, Michoacán, Mexico
Auxilio Mutuo Cancer Center ( Site 3900)
San Juan, , Puerto Rico
Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 4401)
Moreletapark, Gauteng, South Africa
Groote Schuur Hospital ( Site 4400)
Cape Town, Western Cape, South Africa
Haemalife ( Site 4407)
Kuilsriver, Western Cape, South Africa
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)
L'Hospitalet Del Llobregat, Barcelona, Spain
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)
Pozuelo de Alarcón, Madrid, Spain
HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)
Valencia, Valenciana, Comunitat, Spain
Namik Kemal University Medical Faculty-Hematology ( Site 4912)
Tekirdağ, Tekirdas, Turkey (Türkiye)
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)
Ankara, , Turkey (Türkiye)
Mega Medipol-Hematology ( Site 4904)
Istanbul, , Turkey (Türkiye)
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)
Istanbul, , Turkey (Türkiye)
Ege Universitesi Hastanesi ( Site 4902)
Izmir, , Turkey (Türkiye)
City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)
Nottingham, England, United Kingdom
University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)
London-Camden, London, City of, United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-1026-010
Identifier Type: OTHER
Identifier Source: secondary_id
BELLWAVE-010
Identifier Type: OTHER
Identifier Source: secondary_id
2022-501560-17-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1281-1520
Identifier Type: REGISTRY
Identifier Source: secondary_id
1026-010
Identifier Type: -
Identifier Source: org_study_id