Actively Recruiting
A Phase 3, Open-label, Randomized Study Comparing Nemtabrutinib Plus Venetoclax to Venetoclax Plus Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma After Prior Therapy
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-18
735
Participants Needed
54
Research Sites
160 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This research evaluates the combination of nemtabrutinib and venetoclax compared to venetoclax plus rituximab in people with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy. The study aims to assess safety, tolerability, and confirm dosing, focusing on whether the nemtabrutinib plus venetoclax combination improves progression-free survival compared to the standard regimen. The trial is a Phase 3, open-label, randomized study led by Merck Sharp & Dohme LLC. Participants are randomly assigned to one of two groups. One group receives daily oral nemtabrutinib tablets starting from the first cycle day 1 and daily oral venetoclax starting from cycle 2 day 1, continuing for up to two years or until disease progression or discontinuation. The other group receives daily oral venetoclax starting from cycle 1 day 1 and intravenous rituximab once per 28-day cycle beginning cycle 2 day 1 for six cycles, also continuing up to two years or until progression or discontinuation. Each treatment cycle lasts four weeks. During the study, participants undergo regular monitoring for dose-limiting toxicities, adverse events, and reasons for treatment discontinuation. Progression-free survival will be assessed by a blinded independent central review over approximately 71 months. Additional evaluations include minimal residual disease in bone marrow, overall survival, objective response rates, and duration of response, with safety followed for up to 28 months. Participants must meet specific health and disease criteria, and the total study duration extends to July 2035.
CONDITIONS
Brief Title
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).
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma with active disease requiring therapy
- Relapsed or refractory to at least one prior therapy
- At least one marker of disease burden
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization
- Life expectancy of at least 3 months
- Ability to swallow and retain oral medication
- Participants positive for hepatitis B surface antigen if on antiviral therapy for at least 4 weeks and with undetectable viral load before randomization
- Participants with history of hepatitis C virus infection if viral load is undetectable at screening
- Participants with HIV who meet all eligibility criteria
- Adequate organ function confirmed within 7 days before starting study intervention
- Participants capable of producing sperm agree to eliminate nemtabrutinib for 12 days, venetoclax for 1 month, abstain from penile-vaginal intercourse as usual lifestyle, or use prescribed contraception
- Female participants assigned female sex at birth who are not pregnant or breastfeeding and are not persons of childbearing potential or use effective contraception with negative pregnancy test and abstain from breastfeeding
You will not qualify if you...
- Active hepatitis B or hepatitis C virus infection
- Gastrointestinal dysfunction affecting drug absorption
- Additional malignancy progressing or requiring treatment within past 2 years
- Diagnosis of Richter Transformation or active central nervous system involvement by CLL/SLL
- Active infection needing systemic therapy during screening
- HIV-infected participants with history of Kaposi's sarcoma, Multicentric Castleman's Disease, or AIDS-defining infections within past 12 months
- Clinically significant cardiovascular disease
- Known allergy or contraindication to nemtabrutinib, venetoclax, rituximab, or excipients
- History of severe bleeding disorders
- Prior systemic anticancer therapy within 5 half-lives or 4 weeks if monoclonal antibody before randomization
- Prior B-cell lymphoma 2 inhibitor therapy within 12 months, recent radiotherapy within 2 weeks, or corticosteroid-requiring radiation toxicities
- Current treatment with certain medications affecting drug metabolism
- Live or live attenuated vaccine within 30 days before first dose
- Use of investigational agents or devices within 4 weeks before study intervention
- Psychiatric or substance use disorder interfering with study participation
- Incomplete recovery from major surgery or ongoing surgical complications
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 years or until disease progression or discontinuation
Participants receive oral nemtabrutinib and venetoclax tablets or oral venetoclax tablets plus rituximab intravenous infusions in repeated 4-week cycles. Treatment continues up to 2 years, until disease progression, or discontinuation.
4-week cycles with oral medication daily and rituximab infusions once per cycle for 6 cycles (if assigned)
Trial Site Locations
Total: 54 locations
1
Highlands Oncology Group ( Site 5405)
Springdale, Arkansas, United States, 72762
Actively Recruiting
2
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Long Beach, California, United States, 90806
Actively Recruiting
3
Memorial Hospital West ( Site 5410)
Pembroke Pines, Florida, United States, 33028
Actively Recruiting
4
Oregon Health and Science University ( Site 5425)
Portland, Oregon, United States, 97239-3011
Actively Recruiting
5
Medical Oncology Associates, PS ( Site 5406)
Spokane, Washington, United States, 99208
Actively Recruiting
6
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Madison, Wisconsin, United States, 53792
Completed
7
Instituto Alexander Fleming ( Site 1005)
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
Actively Recruiting
8
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)
Mar del Plata, Buenos Aires, Argentina, B7600FZO
Actively Recruiting
9
Sanatorio Parque ( Site 1003)
Rosario, Santa Fe Province, Argentina, S2000DSV
Actively Recruiting
10
Centro Medico Fleischer ( Site 1006)
Buenos Aires, Argentina, 1414
Actively Recruiting
11
Hospital Aleman-oncohematologic diseases ( Site 1001)
Buenos Aires, Argentina, C1118AAT
Actively Recruiting
12
Royal Adelaide Hospital ( Site 1104)
Adelaide, South Australia, Australia, 5000
Actively Recruiting
13
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)
Melbourne, Victoria, Australia, 3021
Actively Recruiting
14
UZ Leuven-Hematology ( Site 1200)
Leuven, Vlaams-Brabant, Belgium, 3000
Actively Recruiting
15
ZAS Cadix ( Site 1203)
Antwerp, Belgium, 2030
Actively Recruiting
16
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
São Paulo, Brazil, 01246-000
Active, Not Recruiting
17
The Moncton Hospital ( Site 1414)
Moncton, New Brunswick, Canada, E1C 6Z8
Actively Recruiting
18
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)
Greenfield Park, Quebec, Canada, J4V 2H1
Actively Recruiting
19
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)
Sherbrooke, Quebec, Canada, J1H 5H4
Actively Recruiting
20
Biocenter ( Site 1507)
Concepción, Biobio, Chile, 4070196
Actively Recruiting
21
IC La Serena Research ( Site 1506)
La Serena, Coquimbo Region, Chile, 1720430
Actively Recruiting
22
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
Santiago, Region M. de Santiago, Chile, 7500653
Actively Recruiting
23
FALP-UIDO ( Site 1500)
Santiago, Region M. de Santiago, Chile, 7500921
Actively Recruiting
24
Clínica Inmunocel ( Site 1511)
Santiago, Region M. de Santiago, Chile, 7580206
Actively Recruiting
25
Fundación Valle del Lili ( Site 1703)
Cali, Valle del Cauca Department, Colombia, 760032
Actively Recruiting
26
Hopital Claude Huriez - CHU de Lille ( Site 2107)
Lille, Nord, France, 59037
Actively Recruiting
27
Centre Hospitalier Universitaire Estaing ( Site 2105)
Clermont-Ferrand, Puy-de-Dome, France, 63100
Actively Recruiting
28
CHD Vendee ( Site 2100)
La Roche-sur-Yon, Vendee, France, 85925
Actively Recruiting
29
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)
Trier, Rhineland-Palatinate, Germany, 54290
Actively Recruiting
30
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)
Leipzig, Saxony, Germany, 04103
Actively Recruiting
31
Rambam Health Care Campus ( Site 2801)
Haifa, Israel, 3109601
Actively Recruiting
32
Hadassah Medical Center-Hemato-Oncology ( Site 2812)
Jerusalem, Israel, 9112001
Actively Recruiting
33
Sheba Medical Center-Hemato Oncology ( Site 2809)
Ramat Gan, Israel, 5265601
Actively Recruiting
34
Sourasky Medical Center ( Site 2811)
Tel Aviv, Israel, 6423906
Actively Recruiting
35
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)
Alessandria, Italy, 15121
Actively Recruiting
36
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)
Milan, Italy, 20132
Actively Recruiting
37
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)
Reggio Emilia, Italy, 42123
Actively Recruiting
38
Centro de Infusion Superare ( Site 3314)
Mexico City, Mexico City, Mexico, 03100
Actively Recruiting
39
Health Pharma Professional Research S.A. de C.V: ( Site 3301)
Mexico City, Mexico City, Mexico, 03100
Actively Recruiting
40
Centro de Investigacion Clinica Chapultepec ( Site 3309)
Morelia, Michoacán, Mexico, 58260
Actively Recruiting
41
Auxilio Mutuo Cancer Center ( Site 3900)
San Juan, Puerto Rico, 00918
Actively Recruiting
42
Alberts Cellular Therapy. ( Site 4401)
Pretoria, Gauteng, South Africa, 0181
Actively Recruiting
43
Groote Schuur Hospital ( Site 4400)
Cape Town, Western Cape, South Africa, 7925
Actively Recruiting
44
Haemalife ( Site 4407)
Kuilsriver, Western Cape, South Africa, 7580
Actively Recruiting
45
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)
L'Hospitalet Del Llobregat, Barcelona, Spain, 08908
Actively Recruiting
46
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)
Pozuelo de Alarcón, Madrid, Spain, 28223
Actively Recruiting
47
HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)
Valencia, Valenciana, Comunitat, Spain, 46010
Actively Recruiting
48
Ege Universitesi Hastanesi ( Site 4902)
Bornova, İzmir, Turkey (Türkiye), 35100
Actively Recruiting
49
Namik Kemal University Medical Faculty-Hematology ( Site 4912)
Tekirdağ, Tekirdas, Turkey (Türkiye), 59100
Actively Recruiting
50
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)
Ankara, Turkey (Türkiye), 06100
Completed
51
Mega Medipol-Hematology ( Site 4904)
Istanbul, Turkey (Türkiye), 34214
Actively Recruiting
52
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)
Istanbul, Turkey (Türkiye), 34722
Actively Recruiting
53
City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)
Nottingham, England, United Kingdom, NG5 1PF
Actively Recruiting
54
University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)
London-Camden, London, City of, United Kingdom, NW1 2PG
Actively Recruiting
Research Team
T
Toll Free Number
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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