Leukemia, Lymphocytic, Chronic, B-CellPhase 3NCT05947851
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 study testing Nemtabrutinib, Venetoclax and Rituximab in people with Leukemia, Lymphocytic, Chronic, B-Cell and Leukemia, Chronic Lymphocytic, run by Merck Sharp & Dohme LLC at 99 sites in 22 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic, Small-Cell Lymphoma
- What is being tested?
- Nemtabrutinib, Venetoclax and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 735 participants
- Where
- 99 sitesin 22 countries
- Study dates
- 8 Aug 2023to 1 Jul 2035
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
99 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
99 sites in 22 countries
United States25 sites, 24 recruiting
- Recruiting
Avera Cancer Institute - Aberdeen ( Site 5458)
Aberdeen, South Dakota, 57401
Study Coordinator, 605-601-1830
- Recruiting
New York Oncology Hematology, P.C. ( Site 5453)
Albany, New York, 12208
Study Coordinator, 518-262-6696
- Recruiting
Center for Cancer and Blood Disorders ( Site 5439)
Bethesda, Maryland, 20817
Study Coordinator, 301-571-2016
- Recruiting
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433)
Billings, Montana, 59102
Study Coordinator, 406-238-6685
- Recruiting
University of Virginia Cancer Center ( Site 5402)
Charlottesville, Virginia, 22903
Study Coordinator, 434-924-9333
- Recruiting
Clermont Oncology Center ( Site 5430)
Clermont, Florida, 34711
Study Coordinator, 386-538-3169
- Recruiting
Fort Wayne Medical Oncology and Hematology ( Site 5444)
Fort Wayne, Indiana, 46804
Study Coordinator, 260-436-0800
- Recruiting
Hattiesburg Clinic Hematology/Oncology ( Site 5416)
Hattiesburg, Mississippi, 39401
Study Coordinator, 601-261-1700
- Recruiting
MidAmerica Cancer Care, LLC ( Site 5426)
Kansas City, Missouri, 64132
Study Coordinator, 816-974-5050
- Recruiting
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Long Beach, California, 90806
Study Coordinator, 562-933-7866
- Completed
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Madison, Wisconsin, 53792
- Recruiting
Avera Cancer Institute - Marshall ( Site 5462)
Marshall, Minnesota, 56258
Study Coordinator, 605-601-1830
- Recruiting
Avera Cancer Institute - Mitchell ( Site 5461)
Mitchell, South Dakota, 57301
Study Coordinator, 605-322-3299
- Recruiting
West Virginia University ( Site 5447)
Morgantown, West Virginia, 26506
Study Coordinator, 304-598-4500
- Recruiting
Atlantic Health System Morristown Medical Center ( Site 5445)
Morristown, New Jersey, 07960
Study Coordinator, 973-971-5000
- Recruiting
Vista Oncology ( Site 5449)
Olympia, Washington, 98506
Study Coordinator, 360-413-8880
- Recruiting
Memorial Hospital West ( Site 5410)
Pembroke Pines, Florida, 33028
Study Coordinator, 954-844-8318
- Recruiting
Avera Cancer Institute - Pierre ( Site 5460)
Pierre, South Dakota, 57501
Study Coordinator, 605-601-1830
- Recruiting
Oregon Health and Science University ( Site 5425)
Portland, Oregon, 97239-3011
Study Coordinator, 503-494-5058
- Recruiting
Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434)
Reno, Nevada, 89502
Study Coordinator, 775-982-4000
- Recruiting
Avera Cancer Institute- Research ( Site 5437)
Sioux Falls, South Dakota, 57105
Study Coordinator, 605-322-3035
- Recruiting
Medical Oncology Associates, PS ( Site 5406)
Spokane, Washington, 99208
Study Coordinator, 509-462-2273
- Recruiting
Highlands Oncology Group ( Site 5405)
Springdale, Arkansas, 72762
Study Coordinator, 479-872-8130
- Recruiting
PatientCare Clinical Research LLC ( Site 5435)
Sugar Land, Texas, 77479
Study Coordinator, 929-712-7467
- Recruiting
Avera Cancer Institute - Yankton ( Site 5459)
Yankton, South Dakota, 57078
Study Coordinator, 605-601-1830
Japan7 sites, 7 recruiting
- Recruiting
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital ( Site 3006)
Hiroshima, 730-8619
Study Coordinator, +81-82-241-3111
- Recruiting
Cancer Institute Hospital of JFCR ( Site 3003)
Koto, Tokyo, 135-8550
Study Coordinator, +81-3-3520-0111
- Recruiting
Nagasaki University Hospital ( Site 3008)
Nagasaki, 852-8501
Study Coordinator, +81-95-819-7200
- Recruiting
Kochi Medical School Hospital ( Site 3007)
Nankoku, Kochi, 783-8505
Study Coordinator, +81-88-866-5811
- Recruiting
National Hospital Organization Osaka National Hospital ( Site 3004)
Osaka, 540-0006
Study Coordinator, +81-6-6942-1331
- Recruiting
Kindai University Hospital ( Site 3005)
Sakai, Osaka, 590-0197
Study Coordinator, +81-72-288-7222
- Recruiting
Yamagata University Hospital ( Site 3002)
Yamagata, 990-9585
Study Coordinator, +81-23-633-1122
Argentina6 sites, 6 recruiting
- Recruiting
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002)
Buenos Aires, Buenos Aires F.D., C1431FWO
Study Coordinator, +541152991200
- Recruiting
Centro Medico Fleischer ( Site 1006)
Buenos Aires, 1414
Study Coordinator, +541148544097
- Recruiting
Hospital Aleman-oncohematologic diseases ( Site 1001)
Buenos Aires, C1118AAT
Study Coordinator, +541148277000
- Recruiting
Instituto Alexander Fleming ( Site 1005)
Ciudad Autónoma de Buenos Aires, Buenos Aires, C1426ANZ
Study Coordinator, +541132218900
- Recruiting
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)
Mar del Plata, Buenos Aires, B7600FZO
Study Coordinator, +542234963224
- Recruiting
Sanatorio Parque ( Site 1003)
Rosario, Santa Fe Province, S2000DSV
Study Coordinator, +543414200222
Turkey (Türkiye)6 sites, 5 recruiting
- Completed
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)
Ankara, 06100
- Recruiting
Ege Universitesi Hastanesi ( Site 4902)
Bornova, İzmir, 35100
Study Coordinator, +905325566128
- Recruiting
Mega Medipol-Hematology ( Site 4904)
Istanbul, 34214
Study Coordinator, 0212 444 70 44
- Recruiting
Sisli Florence Nightingale Hastanesi ( Site 4916)
Istanbul, 34381
Study Coordinator, 905348310606
- Recruiting
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)
Istanbul, 34722
Study Coordinator, 0090 216 606 52 00
- Recruiting
Namik Kemal University Medical Faculty-Hematology ( Site 4912)
Tekirdağ, Tekirdas, 59100
Study Coordinator, 0090 282 250 50 50
Chile5 sites, 5 recruiting
- Recruiting
Biocenter ( Site 1507)
Concepción, Biobio, 4070196
Study Coordinator, +56412858421
- Recruiting
IC La Serena Research ( Site 1506)
La Serena, Coquimbo Region, 1720430
Study Coordinator, +56958646664
- Recruiting
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
Santiago, Region M. de Santiago, 7500653
Study Coordinator, +56991612199
- Recruiting
FALP-UIDO ( Site 1500)
Santiago, Region M. de Santiago, 7500921
Study Coordinator, 56224205098
- Recruiting
Clínica Inmunocel ( Site 1511)
Santiago, Region M. de Santiago, 7580206
Study Coordinator, +56224376600
Greece4 sites, 4 recruiting
- Recruiting
GENERAL HOSPITAL OF ALEXANDROUPOLI ( Site 2310)
Alexandroupoli, East Macedonia and Thrace, 681 00
Study Coordinator, +302551030320
- Recruiting
Evangelismos General Hospital of Athens ( Site 2302)
Athens, Attica, 106 76
Study Coordinator, 0030 2132041721
- Recruiting
General Hospital of Athens "Laiko" ( Site 2308)
Athens, Attica, 115 27
Study Coordinator, +302132061702
- Recruiting
General Hospital of Athens "Laiko" ( Site 2309)
Athens, Attica, 115 27
Study Coordinator, 0030 2132061643
Israel4 sites, 4 recruiting
- Recruiting
Rambam Health Care Campus ( Site 2801)
Haifa, 3109601
Study Coordinator, +97247771514
- Recruiting
Hadassah Medical Center-Hemato-Oncology ( Site 2812)
Jerusalem, 9112001
Study Coordinator, +972-539101736
- Recruiting
Sheba Medical Center-Hemato Oncology ( Site 2809)
Ramat Gan, 5265601
Study Coordinator, +972-35308401
- Recruiting
Sourasky Medical Center ( Site 2811)
Tel Aviv, 6423906
Study Coordinator, +97237772649
New Zealand4 sites, 4 recruiting
- Recruiting
North Shore Hospital-Department of Haematology ( Site 3505)
Auckland, 0622
Study Coordinator, +6494868920x49725
- Recruiting
Aotearoa Clinical Trials ( Site 3504)
Auckland, 2025
Study Coordinator, +6433640386
- Recruiting
Christchurch Hospital ( Site 3503)
Christchurch, Canterbury, 8011
Study Coordinator, +6433640386
- Recruiting
Palmerston North Hospital ( Site 3506)
Palmerston North, Manawatu-Wanganui, 4414
Study Coordinator, +6463509169
Taiwan4 sites, 4 recruiting
- Recruiting
Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 4700)
Kaohsiung City, 83301
Study Coordinator, +88677317123
- Recruiting
National Cheng Kung University Hospital ( Site 4701)
Tainan, 704
Study Coordinator, +88662353535
- Recruiting
National Taiwan University Hospital ( Site 4704)
Taipei, 10048
Study Coordinator, +886223123456
- Recruiting
Tri-Service General Hospital-hematology&oncology ( Site 4703)
Taipei City, Taipei, 114
Study Coordinator, +886287923311
Australia3 sites, 3 recruiting
- Recruiting
Royal Adelaide Hospital ( Site 1104)
Adelaide, South Australia, 5000
Study Coordinator, +61870740000
- Recruiting
Box Hill Hospital ( Site 1106)
Box Hill, Victoria, 3128
Study Coordinator, +61438659719
- Recruiting
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)
Melbourne, Victoria, 3021
Study Coordinator, +61383959130
Canada3 sites, 3 recruiting
- Recruiting
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)
Greenfield Park, Quebec, J4V 2H1
Study Coordinator, 450-466-5000 x3226
- Recruiting
The Moncton Hospital ( Site 1414)
Moncton, New Brunswick, E1C 6Z8
Study Coordinator, 506-870-2404
- Recruiting
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)
Sherbrooke, Quebec, J1H 5H4
Study Coordinator, 819-346-1110 x12811
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Universitaire Estaing ( Site 2105)
Clermont-Ferrand, Puy-de-Dome, 63100
Study Coordinator, +33473750065
- Recruiting
CHD Vendee ( Site 2100)
La Roche-sur-Yon, Vendee, 85925
Study Coordinator, +33251446572
- Recruiting
Hopital Claude Huriez - CHU de Lille ( Site 2107)
Lille, Nord, 59037
Study Coordinator, +333 20 44 59 62
Germany3 sites, 3 recruiting
- Recruiting
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)
Leipzig, Saxony, 04103
Study Coordinator, +49 341 97 13131
- Recruiting
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)
Trier, Rhineland-Palatinate, 54290
Study Coordinator, +496519472571
- Recruiting
Universitaetsklinikum Ulm. ( Site 2206)
Ulm, Baden-Wurttemberg, 89081
Study Coordinator, +497315000
Italy3 sites, 3 recruiting
- Recruiting
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)
Alessandria, 15121
Study Coordinator, +390131206440
- Recruiting
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)
Milan, 20132
Study Coordinator, +390226436119
- Recruiting
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)
Reggio Emilia, 42123
Study Coordinator, +390522295654
Mexico3 sites, 3 recruiting
- Recruiting
Centro de Infusion Superare ( Site 3314)
Mexico City, Mexico City, 03100
Study Coordinator, +52 55 5264 6440
- Recruiting
Health Pharma Professional Research S.A. de C.V: ( Site 3301)
Mexico City, Mexico City, 03100
Study Coordinator, +52 55 7586 4856
- Recruiting
Centro de Investigacion Clinica Chapultepec ( Site 3309)
Morelia, Michoacán, 58260
Study Coordinator, +52 443 147 8545
South Africa3 sites, 3 recruiting
- Recruiting
Groote Schuur Hospital ( Site 4400)
Cape Town, Western Cape, 7925
Study Coordinator, +27727689024
- Recruiting
Haemalife ( Site 4407)
Kuilsriver, Western Cape, 7580
Study Coordinator, +27 21 900 6277
- Recruiting
Alberts Cellular Therapy. ( Site 4401)
Pretoria, Gauteng, 0181
Study Coordinator, +27 12 993 2555
Spain3 sites, 3 recruiting
- Recruiting
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)
L'Hospitalet Del Llobregat, Barcelona, 08908
Study Coordinator, +34932607750
- Recruiting
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)
Pozuelo de Alarcón, Madrid, 28223
Study Coordinator, 914521900
- Recruiting
HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)
Valencia, Valenciana, Comunitat, 46010
Study Coordinator, 961973930
Belgium2 sites, 2 recruiting
- Recruiting
ZAS Cadix ( Site 1203)
Antwerp, 2030
Study Coordinator, +32 3/339 76 38
- Recruiting
UZ Leuven-Hematology ( Site 1200)
Leuven, Vlaams-Brabant, 3000
Study Coordinator, +32 16/338544
Brazil2 sites, 1 recruiting
- Active, not recruiting
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
São Paulo, 01246-000
- Recruiting
Hospital Paulistano-Americas Oncologia ( Site 1302)
São Paulo, 01321-001
Study Coordinator, +5511992926463
Colombia2 sites, 2 recruiting
- Recruiting
Fundación Valle del Lili ( Site 1703)
Cali, Valle del Cauca Department, 760032
Study Coordinator, 57 3133288646
- Recruiting
Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707)
Medellín, Antioquia, 050030
Study Coordinator, +576044480016Ext2204
Puerto Rico2 sites, 2 recruiting
- Recruiting
BRCR Global Puerto Rico - Hato Rey ( Site 3901)
San Juan, 00917
Study Coordinator, +17875612375195
- Recruiting
Auxilio Mutuo Cancer Center ( Site 3900)
San Juan, 00918
Study Coordinator, 7877582000
United Kingdom2 sites, 2 recruiting
- Recruiting
University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)
London-Camden, London, City of, NW1 2PG
Study Coordinator, +4420 3447 2528
- Recruiting
City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)
Nottingham, England, NG5 1PF
Study Coordinator, +44115969116972549
About this study
Official title: 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)
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).
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic, Small-Cell Lymphoma, Lymphoma, Small Lymphocytic, CLL, SLL
- Being tested
- Nemtabrutinib, Venetoclax, Rituximab
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NemtabrutinibDrug
Also called ARQ 531, MK-1026
5, 20, and 45 tablets
VenetoclaxDrug
Also called ABT-199, GDC-0199
10, 50, and 100 mg tablets
RituximabBiological
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
| Study group | Role | What they receive |
|---|---|---|
| Nemtabrutinib + Venetoclax | Experimental | 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. Receives: Drug: Nemtabrutinib; Drug: Venetoclax |
| Venetoclax + Rituximab | Active comparator | 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. Receives: Drug: Venetoclax; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLT evaluation period is defined as 8 weeks after the first dose of the combination treatment of nemtabrutinib plus venetoclax Cycle 2 Day 1 in Part 1 + 4 weeks follow up. Each cycle is 4 weeks. DLTs are: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting >7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week (with exceptions); missing >25% of nemtabrutinib or venetoclax doses as a result of drug-related adverse events during the first 2 cycles; Grade 5 toxicity.
Measured: Up to approximately 12 Weeks
Part 1: Number of Participants Experiencing Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1.
Measured: Up to approximately 28 months
Part 1: Number of Participants Discontinuing Study Treatment Due to AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported for Part 1.
Measured: Up to approximately 25 months
Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization to the first documented disease progression per iwCLL criteria 2018 as accessed by BICR, or death due to any cause, whichever occurs first. PFS will be presented.
Measured: Up to approximately 71 months
Secondary outcomes (6)
Part 2: Undetectable Minimal Residual Disease (MRD) Rate in Bone Marrow as Assessed by Central Laboratory
Undetectable MRD, defined as <1 leukemic cell per 10,000 cells (MRD <10-4) in bone marrow. The MRD rate will be presented.
Measured: Up to approximately 46 months
Part 2: Overall Survival (OS)
OS, defined as the time from randomization to death due to any cause. OS will be presented.
Measured: Up to approximately 108 months
Part 2: Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR
OR, defined as complete response/remission (CR), complete response with incomplete count recovery (CRi), nodular partial remission (nPR), or partial remission (PR). CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow. ORR will be presented.
Measured: Up to approximately 71 months
Part 2: Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR
DOR, defined as the time from the first documented evidence of CR, CRi, nPR, or PR that led to response until disease progression or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow. DOR will be presented.
Measured: Up to approximately 108 months
Part 2: Number of Participants Experiencing AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 2.
Measured: Up to approximately 28 months
Part 2: Number of Participants Discontinuing Study Treatment Due to AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported for Part 2.
Measured: Up to approximately 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2023
- Study start8 Aug 2023
- Primary completion1 Jun 2032 (estimated)
- Study completion1 Jul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In Part 1, Dose Confirmation will be determined by modified toxicity probability interval (mTPI) design, where participants will be assigned to two treatment groups, Nemtabrutinib + Venetoclax in parallel with Nemtabrutinib + Venetoclax. Part 2 will be an Efficacy Expansion where all participants will be randomized 1:1 to Nemtabrutinib Part 1 Dose Selection plus Venetoclax or Venetoclax plus Rituximab (VR) (or Rituximab biosimilar) for the duration of the study.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 735 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05947851
- Sponsor's protocol ID
- 1026-010
- Other IDs
- MK-1026-010, BELLWAVE-010, 2022-501560-17-00, U1111-1281-1520, jRCT2061260028
- Status last verified
- Oct 2026
- First submitted
- 7 Jul 2023
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf