A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)

NCT05624554 | Active Not Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: 1026-0082022-501481-21-00MK-1026-008U1111-1274-25742021-006593-23
• Study Type: interventional
• Target: 300
• Locations: 21 countries
• Sites: 97

Brief Summary

Researchers are looking for new ways to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). CLL and SLL are types of blood cancer. Researchers want to know if people who take nemtabrutinib compared to those who take the standard treatments in this study will live longer without their cancer growing, spreading or returning (progression free survival).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR)

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD is evaluated per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by blinded independent central review (BICR).

  Up to approximately 49 months

Secondary Outcomes (6)

• Overall Survival (OS)

  Up to approximately 94 months

• Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR

  Up to approximately 36 months

• Time to Next Therapy (TTNT)

  Up to approximately 94 months

• Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR

  Up to approximately 94 months

• Number of Participants Who Experience an Adverse Event (AE)

  Up to approximately 94 months

Study Arms (2)

Nemtabrutinib

EXPERIMENTAL

Administered daily via oral tablet.

Drug: Nemtabrutinib

FCR or BR

ACTIVE COMPARATOR

Investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) OR bendamustine plus rituximab (BR). Participants will receive either rituximab or specified approved rituximab biosimilar.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Bendamustine; Biological: Rituximab; Biological: Truxima; Biological: Ruxience; Biological: Riabni

Interventions

Nemtabrutinib DRUG

65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met.

Also known as: MK-1026, ARQ 531

Nemtabrutinib

Fludarabine DRUG

25 mg/m\^2 administered via intravenous (IV) infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles.

FCR or BR

Cyclophosphamide DRUG

250 mg/m\^2 administered via IV infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles.

FCR or BR

Bendamustine DRUG

Administered via IV infusion on Days 1 and 2 of each 28-day cycle up to 6 cycles. The first dose is given as 70 to 90 mg/m\^2. Subsequent doses may be escalated up to 90 mg/m\^2, if applicable and as per local guidelines.

FCR or BR

Rituximab BIOLOGICAL

Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles.

Also known as: RITUXAN®/MabThera

FCR or BR

Truxima BIOLOGICAL

Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles.

Also known as: Rituximab biosimilar

FCR or BR

Ruxience BIOLOGICAL

Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles.

Also known as: Rituximab biosimilar

FCR or BR

Riabni BIOLOGICAL

Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles.

Also known as: Rituximab biosimilar

FCR or BR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Confirmed diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and active disease clearly documented to have a need to initiate therapy
• Has previously untreated CLL/SLL participants without tumor protein 53 (TP53) aberrations and documented 11q status and immunoglobulin heavy chain gene (IGHV) mutational status
• The ability to swallow and retain oral medication
• Has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Has gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy
• Has history of severe bleeding disorders
• Has not adequately recovered from major surgery or has ongoing surgical complications

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (97)

Highlands Oncology Group ( Site 5205)

Springdale, Arkansas, 72762, United States

Location

Clermont Oncology Center ( Site 5224)

Clermont, Florida, 34711, United States

Location

Hattiesburg Clinic Hematology/Oncology ( Site 5216)

Hattiesburg, Mississippi, 39401, United States

Location

Medical Oncology Associates, PS ( Site 5206)

Spokane, Washington, 99208, United States

Location

Royal Adelaide Hospital ( Site 1105)

Adelaide, South Australia, 5000, Australia

Location

Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1317)

Curitiba, Paraná, 81520-060, Brazil

Location

Hospital Amaral Carvalho-Centro de Pesquisas ( Site 1304)

Jaú, São Paulo, 17210-120, Brazil

Location

A. C. Camargo Cancer Center ( Site 1318)

São Paulo, São Paulo, 01525-001, Brazil

Location

Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( Site 1319)

Rio de Janeiro, 20231-050, Brazil

Location

ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)

São Paulo, 01246-000, Brazil

Location

Hospital Paulistano-Americas Oncologia ( Site 1302)

São Paulo, 01321-001, Brazil

Location

Specialized Hospital for Active Treatment of Haematology Diseases ( Site 6403)

Sofia, Sofia (stolitsa), 1797, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD ( Site 6404)

Plovdiv, 4002, Bulgaria

Location

Medical Centre Pratia Clinic EOOD ( Site 6406)

Plovdiv, 4003, Bulgaria

Location

UMHAT "Prof. Dr. Stoyan Kirkovich"AD-Clinical Hematology ( Site 6400)

Stara Zagora, 6003, Bulgaria

Location

Multriprofile Hospital for Active Treatment "Hristo Botev" ( Site 6402)

Vratsa, 3000, Bulgaria

Location

IC La Serena Research ( Site 1506)

La Serena, Coquimbo Region, 1720430, Chile

Location

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)

Santiago, Region M. de Santiago, 7500653, Chile

Location

FALP-UIDO ( Site 1500)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Clínica Inmunocel ( Site 1511)

Santiago, Region M. de Santiago, 7580206, Chile

Location

James Lind Centro de Investigacion del Cancer ( Site 1503)

Temuco, Región de la Araucanía, 4800827, Chile

Location

Biocenter ( Site 1507)

Concepción, Región del Biobío, 4070196, Chile

Location

Peking University Third Hospital ( Site 1602)

Beijing, Beijing Municipality, 100191, China

Location

Chongqing University Cancer Hospital ( Site 1605)

Chongqing, Chongqing Municipality, 400030, China

Location

Chongqing University Three Gorges Hospital ( Site 1609)

Chongqing, Chongqing Municipality, 404000, China

Location

Southern Medical University Nanfang Hospital-Department of Hematopathology ( Site 1607)

Guangzhou, Guangdong, 510515, China

Location

Sun Yat-sen University Cancer Center ( Site 1608)

Guangzhou, Guangdong, 510700, China

Location

The Affiliated Hospital of Guizhou Medical University ( Site 1625)

Guiyang, Guizhou, 550004, China

Location

Hainan General Hospital ( Site 1603)

Haikou, Hainan, 570311, China

Location

Henan Cancer Hospital-hematology department ( Site 1613)

Zhengzhou, Henan, 450008, China

Location

Tongji Hospital Tongji Medical,Science & Technology ( Site 1619)

Wuhan, Hubei, 430000, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1618)

Wuhan, Hubei, 430022, China

Location

Xiangya Hospital Central South University-Hematology department ( Site 1616)

Changsha, Hunan, 410008, China

Location

Hunan Cancer Hospital ( Site 1615)

Changsha, Hunan, 410013, China

Location

The First Affiliated Hospital of Soochow University-hematology department ( Site 1612)

Suzhou, Jiangsu, 215006, China

Location

The First Affiliated Hospital of Nanchang University ( Site 1614)

Nanchang, Jiangxi, 330006, China

Location

Jiangxi Provincial Cancer Hospital ( Site 1628)

Nanchang, Jiangxi, 330029, China

Location

The First Hospital of Jilin University-Hematology ( Site 1621)

Changchun, Jilin, 130021, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1617)

Xi'an, Shaanxi, 710061, China

Location

Shaanxi provincial people's hospital ( Site 1626)

Xi'an, Shaanxi, 710068, China

Location

Fudan University Shanghai Cancer Center ( Site 1606)

Shanghai, Shanghai Municipality, 200032, China

Location

Shanxi Cancer Hospital ( Site 1629)

Taiyuan, Shanxi, 030000, China

Location

Institute of hematology&blood disease hospital ( Site 1600)

Tianjin, Tianjin Municipality, 300020, China

Location

Tianjin Medical University Cancer Institute & Hospital-lymphoma ( Site 1604)

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital, Zhejiang University-Hematology ( Site 1611)

Hangzhou, Zhejiang, 310003, China

Location

Clini Salud ( Site 1700)

Envigado, Antioquia, 055422, Colombia

Location

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707)

Medellín, Antioquia, 050030, Colombia

Location

Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1704)

Valledupar, Cesar Department, 200001, Colombia

Location

Oncologos del Occidente ( Site 1706)

Pereira, Risaralda Department, 660001, Colombia

Location

Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 1902)

Aarhus, Central Jutland, 8200, Denmark

Location

Aalborg Universitetshospital, Syd ( Site 1901)

Aalborg, North Denmark, 9000, Denmark

Location

Odense Universitetshospital ( Site 1900)

Odense C, Region Syddanmark, 5000, Denmark

Location

Vejle Sygehus ( Site 1903)

Vejle, Region Syddanmark, 7100, Denmark

Location

MEDI-K ( Site 2401)

Guatemala City, 01009, Guatemala

Location

CELAN,S.A ( Site 2403)

Guatemala City, 01010, Guatemala

Location

Oncomedica ( Site 2402)

Guatemala City, 01010, Guatemala

Location

Queen Mary Hospital ( Site 2500)

Hksar, Hong Kong

Location

Fejér Megyei Szent György Egyetemi Oktató Kórház ( Site 2609)

Székesfehérvár, Fejér, 8000, Hungary

Location

Heves Vármegyei Markhot Ferenc Oktatókórház és Rendelőintézet ( Site 2608)

Eger, Heves County, 3300, Hungary

Location

Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 2602)

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Hospital of Lithuanian University of Health Sciences Kauno klinikos-Oncology and Hematology ( Site 3100)

Kaunas, Kaunas County, 50161, Lithuania

Location

Hospital Sultanah Aminah ( Site 3203)

Johor Bahru, Johor, 80100, Malaysia

Location

Hospital Ampang ( Site 3202)

Ampang, Selangor, 68000, Malaysia

Location

Centro de Infusion Superare ( Site 3314)

Mexico City, Mexico City, 03100, Mexico

Location

Health Pharma Professional Research S.A. de C.V: ( Site 3301)

Mexico City, Mexico City, 03100, Mexico

Location

Centro de Investigacion Clinica Chapultepec ( Site 3309)

Morelia, Michoacán, 58260, Mexico

Location

Oaxaca Site Management Organization ( Site 3313)

Oaxaca City, 68000, Mexico

Location

Uniwersytecki Szpital Kliniczny nr 1 w Lublinie ( Site 3710)

Lublin, Lublin Voivodeship, 20-081, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 3701)

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 3702)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Pratia Onkologia Katowice ( Site 3705)

Katowice, Silesian Voivodeship, 40-519, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmi-Oddzial Kliniczny Hematologii ( Site 3704)

Olsztyn, Warmian-Masurian Voivodeship, 10-228, Poland

Location

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 3711)

Kielce, Świętokrzyskie Voivodeship, 25-734, Poland

Location

Spitalul Clinic Colțea ( Site 4000)

Bucharest, București, 030171, Romania

Location

Spitalul Clinic Colțea ( Site 4001)

Bucharest, București, 030171, Romania

Location

Institutul Oncologic Cluj ( Site 4002)

Cluj-Napoca, 400015, Romania

Location

National Cancer Centre Singapore ( Site 4200)

Singapore, Central Singapore, 168583, Singapore

Location

Tan Tock Seng Hospital ( Site 4202)

Singapore, Central Singapore, 308433, Singapore

Location

Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 4401)

Centurion, Gauteng, 0181, South Africa

Location

Wits Clinical Research ( Site 4403)

Johannesburg, Gauteng, 1864, South Africa

Location

Groote Schuur Hospital-Clinical Haematology ( Site 4400)

Cape Town, Western Cape, 7925, South Africa

Location

Haemalife ( Site 4407)

Kuilsriver, Western Cape, 7580, South Africa

Location

Constantiaberg Haematology ( Site 4408)

Plumstead, Western Cape, 7800, South Africa

Location

Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 4700)

Kaohsiung City, 83301, Taiwan

Location

National Cheng Kung University Hospital ( Site 4701)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 4704)

Taipei, 10002, Taiwan

Location

Mega Medipol-Hematology ( Site 4904)

Stanbul, Istanbul, 34214, Turkey (Türkiye)

Location

Namik Kemal University Medical Faculty-Hematology ( Site 4912)

Suleymanpasa, Tekirdas, 59100, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)

Ankara, 06100, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)

Istanbul, 34722, Turkey (Türkiye)

Location

Ege Universitesi Hastanesi ( Site 4902)

Izmir, 35100, Turkey (Türkiye)

Location

MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 5106)

Cherkassy, Cherkasy Oblast, 18009, Ukraine

Location

Communal non-profit enterprise "Regional clinical hospital o-Hematology Department ( Site 5113)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76008, Ukraine

Location

Nonprofit Organization National Cancer Institute ( Site 5103)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

Institute of Blood Pathology and Transfusion Medicine of National Aсademy of Medical Sciences of Ukr ( Site 5105)

Lviv, Lviv Oblast, 79057, Ukraine

Location

SI National Research Center of Radiation Medicine, Hematology, Oncology ( Site 5101)

Kyiv, 03115, Ukraine

Location

Public Non-Profit Enterprise Kyiv City Clinical Hospital #9 -Hematology department #1 ( Site 5111)

Kyiv, 04112, Ukraine

Location

Related Publications (1)

• Davids MS. BRUIN 313 and 314 Trials Open the Door for Noncovalent Bruton Tyrosine Kinase Inhibition as Initial Therapy for Chronic Lymphocytic Leukemia. J Clin Oncol. 2026 Feb 20;44(6):435-439. doi: 10.1200/JCO-25-02691. Epub 2025 Dec 9. No abstract available.

  PMID: 41363770 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ARQ531; fludarabine; Cyclophosphamide; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: November 22, 2022
• Study Start: March 16, 2023
• Primary Completion (Estimated): May 19, 2027
• Study Completion (Estimated): March 17, 2031
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GU (3); BU (5); RO (3); BR (6); SG (2); TW (3); TU (5); UA (6); CO (4); PL (6); CL (6); US (4); DK (4); HK (1); HU (3); LI (1); ME (4); CN (23); MY (2); ZA (5); AU (1)