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)

March 13, 2026 updated by: Merck Sharp & Dohme LLC

A Phase 3, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib Versus Chemoimmunotherapy for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Without TP53 Aberrations

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital ( Site 1105)
  • Brazil
      • Rio de Janeiro, Brazil, 20231-050
        • Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( Site 1319)
      • São Paulo, Brazil, 01246-000
        • ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
      • São Paulo, Brazil, 01321-001
        • Hospital Paulistano-Americas Oncologia ( Site 1302)
    • Paraná
      • Curitiba, Paraná, Brazil, 81520-060
        • Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1317)
    • São Paulo
      • Jaú, São Paulo, Brazil, 17210-120
        • Hospital Amaral Carvalho-Centro de Pesquisas ( Site 1304)
      • São Paulo, São Paulo, Brazil, 01525-001
        • A. C. Camargo Cancer Center ( Site 1318)
  • Bulgaria
      • Plovdiv, Bulgaria, 4002
        • University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD ( Site 6404)
      • Plovdiv, Bulgaria, 4003
        • Medical Centre Pratia Clinic EOOD ( Site 6406)
      • Stara Zagora, Bulgaria, 6003
        • UMHAT "Prof. Dr. Stoyan Kirkovich"AD-Clinical Hematology ( Site 6400)
      • Vratsa, Bulgaria, 3000
        • Multriprofile Hospital for Active Treatment "Hristo Botev" ( Site 6402)
    • Sofia (stolitsa)
      • Sofia, Sofia (stolitsa), Bulgaria, 1797
        • Specialized Hospital for Active Treatment of Haematology Diseases ( Site 6403)
  • Chile
    • Coquimbo Region
      • La Serena, Coquimbo Region, Chile, 1720430
        • IC La Serena Research ( Site 1506)
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 7500653
        • Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
      • Santiago, Region M. de Santiago, Chile, 7500921
        • FALP-UIDO ( Site 1500)
      • Santiago, Region M. de Santiago, Chile, 7580206
        • Clínica Inmunocel ( Site 1511)
    • Región de la Araucanía
      • Temuco, Región de la Araucanía, Chile, 4800827
        • James Lind Centro de Investigacion del Cancer ( Site 1503)
    • Región del Biobío
      • Concepción, Región del Biobío, Chile, 4070196
        • Biocenter ( Site 1507)
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100191
        • Peking University Third Hospital ( Site 1602)
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400030
        • Chongqing University Cancer Hospital ( Site 1605)
      • Chongqing, Chongqing Municipality, China, 404000
        • Chongqing University Three Gorges Hospital ( Site 1609)
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Southern Medical University Nanfang Hospital-Department of Hematopathology ( Site 1607)
      • Guangzhou, Guangdong, China, 510700
        • Sun Yat-sen University Cancer Center ( Site 1608)
    • Guizhou
      • Guiyang, Guizhou, China, 550004
        • The Affiliated Hospital of Guizhou Medical University ( Site 1625)
    • Hainan
      • Haikou, Hainan, China, 570311
        • Hainan General Hospital ( Site 1603)
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Henan Cancer Hospital-hematology department ( Site 1613)
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Tongji Hospital Tongji Medical,Science & Technology ( Site 1619)
      • Wuhan, Hubei, China, 430022
        • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1618)
    • Hunan
      • Changsha, Hunan, China, 410008
        • Xiangya Hospital Central South University-Hematology department ( Site 1616)
      • Changsha, Hunan, China, 410013
        • Hunan Cancer Hospital ( Site 1615)
    • Jiangsu
      • Suzhou, Jiangsu, China, 215006
        • The First Affiliated Hospital of Soochow University-hematology department ( Site 1612)
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • The First Affiliated Hospital of Nanchang University ( Site 1614)
      • Nanchang, Jiangxi, China, 330029
        • Jiangxi Provincial Cancer Hospital ( Site 1628)
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University-Hematology ( Site 1621)
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1617)
      • Xi'an, Shaanxi, China, 710068
        • Shaanxi provincial people's hospital ( Site 1626)
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Fudan University Shanghai Cancer Center ( Site 1606)
    • Shanxi
      • Taiyuan, Shanxi, China, 030000
        • Shanxi Cancer Hospital ( Site 1629)
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300020
        • Institute of hematology&blood disease hospital ( Site 1600)
      • Tianjin, Tianjin Municipality, China, 300060
        • Tianjin Medical University Cancer Institute & Hospital-lymphoma ( Site 1604)
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital, Zhejiang University-Hematology ( Site 1611)
  • Colombia
    • Antioquia
      • Envigado, Antioquia, Colombia, 055422
        • Clini Salud ( Site 1700)
      • Medellín, Antioquia, Colombia, 050030
        • Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707)
    • Cesar Department
      • Valledupar, Cesar Department, Colombia, 200001
        • Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1704)
    • Risaralda Department
      • Pereira, Risaralda Department, Colombia, 660001
        • Oncologos del Occidente ( Site 1706)
  • Denmark
    • Central Jutland
      • Aarhus, Central Jutland, Denmark, 8200
        • Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 1902)
    • North Denmark
      • Aalborg, North Denmark, Denmark, 9000
        • Aalborg Universitetshospital, Syd ( Site 1901)
    • Region Syddanmark
      • Odense C, Region Syddanmark, Denmark, 5000
        • Odense Universitetshospital ( Site 1900)
      • Vejle, Region Syddanmark, Denmark, 7100
        • Vejle Sygehus ( Site 1903)
  • Guatemala
      • Guatemala City, Guatemala, 01009
        • MEDI-K ( Site 2401)
      • Guatemala City, Guatemala, 01010
        • CELAN,S.A ( Site 2403)
      • Guatemala City, Guatemala, 01010
        • Oncomedica ( Site 2402)
  • Hong Kong
      • Hksar, Hong Kong
        • Queen Mary Hospital ( Site 2500)
  • Hungary
    • Fejér
      • Székesfehérvár, Fejér, Hungary, 8000
        • Fejér Megyei Szent György Egyetemi Oktató Kórház ( Site 2609)
    • Heves County
      • Eger, Heves County, Hungary, 3300
        • Heves Vármegyei Markhot Ferenc Oktatókórház és Rendelőintézet ( Site 2608)
    • Szabolcs-Szatmár-Bereg
      • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
        • Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 2602)
  • Lithuania
    • Kaunas County
      • Kaunas, Kaunas County, Lithuania, 50161
        • Hospital of Lithuanian University of Health Sciences Kauno klinikos-Oncology and Hematology ( Site 3100)
  • Malaysia
    • Johor
      • Johor Bahru, Johor, Malaysia, 80100
        • Hospital Sultanah Aminah ( Site 3203)
    • Selangor
      • Ampang, Selangor, Malaysia, 68000
        • Hospital Ampang ( Site 3202)
  • Mexico
      • Oaxaca City, Mexico, 68000
        • Oaxaca Site Management Organization ( Site 3313)
    • Mexico City
      • Mexico City, Mexico City, Mexico, 03100
        • Centro de Infusion Superare ( Site 3314)
      • Mexico City, Mexico City, Mexico, 03100
        • Health Pharma Professional Research S.A. de C.V: ( Site 3301)
    • Michoacán
      • Morelia, Michoacán, Mexico, 58260
        • Centro de Investigacion Clinica Chapultepec ( Site 3309)
  • Poland
    • Lublin Voivodeship
      • Lublin, Lublin Voivodeship, Poland, 20-081
        • Uniwersytecki Szpital Kliniczny nr 1 w Lublinie ( Site 3710)
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 3701)
    • Pomeranian Voivodeship
      • Gdansk, Pomeranian Voivodeship, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 3702)
    • Silesian Voivodeship
      • Katowice, Silesian Voivodeship, Poland, 40-519
        • Pratia Onkologia Katowice ( Site 3705)
    • Warmian-Masurian Voivodeship
      • Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-228
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmi-Oddzial Kliniczny Hematologii ( Site 3704)
    • Świętokrzyskie Voivodeship
      • Kielce, Świętokrzyskie Voivodeship, Poland, 25-734
        • Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 3711)
  • Romania
      • Cluj-Napoca, Romania, 400015
        • Institutul Oncologic Cluj ( Site 4002)
    • București
      • Bucharest, București, Romania, 030171
        • Spitalul Clinic Colțea ( Site 4000)
      • Bucharest, București, Romania, 030171
        • Spitalul Clinic Colțea ( Site 4001)
  • Singapore
    • Central Singapore
      • Singapore, Central Singapore, Singapore, 168583
        • National Cancer Centre Singapore ( Site 4200)
      • Singapore, Central Singapore, Singapore, 308433
        • Tan Tock Seng Hospital ( Site 4202)
  • South Africa
    • Gauteng
      • Centurion, Gauteng, South Africa, 0181
        • Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 4401)
      • Johannesburg, Gauteng, South Africa, 1864
        • Wits Clinical Research ( Site 4403)
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7925
        • Groote Schuur Hospital-Clinical Haematology ( Site 4400)
      • Kuilsriver, Western Cape, South Africa, 7580
        • Haemalife ( Site 4407)
      • Plumstead, Western Cape, South Africa, 7800
        • Constantiaberg Haematology ( Site 4408)
  • Taiwan
      • Kaohsiung City, Taiwan, 83301
        • Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 4700)
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital ( Site 4701)
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital ( Site 4704)
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06100
        • Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)
      • Istanbul, Turkey (Türkiye), 34722
        • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)
      • Izmir, Turkey (Türkiye), 35100
        • Ege Universitesi Hastanesi ( Site 4902)
    • Istanbul
      • Stanbul, Istanbul, Turkey (Türkiye), 34214
        • Mega Medipol-Hematology ( Site 4904)
    • Tekirdas
      • Suleymanpasa, Tekirdas, Turkey (Türkiye), 59100
        • Namik Kemal University Medical Faculty-Hematology ( Site 4912)
  • Ukraine
      • Kyiv, Ukraine, 04112
        • Public Non-Profit Enterprise Kyiv City Clinical Hospital #9 -Hematology department #1 ( Site 5111)
      • Kyiv, Ukraine, 03115
        • SI National Research Center of Radiation Medicine, Hematology, Oncology ( Site 5101)
    • Cherkasy Oblast
      • Cherkassy, Cherkasy Oblast, Ukraine, 18009
        • MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 5106)
    • Ivano-Frankivsk Oblast
      • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76008
        • Communal non-profit enterprise "Regional clinical hospital o-Hematology Department ( Site 5113)
    • Kyivska Oblast
      • Kyiv, Kyivska Oblast, Ukraine, 03022
        • Nonprofit Organization National Cancer Institute ( Site 5103)
    • Lviv Oblast
      • Lviv, Lviv Oblast, Ukraine, 79057
        • Institute of Blood Pathology and Transfusion Medicine of National Aсademy of Medical Sciences of Ukr ( Site 5105)
  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Highlands Oncology Group ( Site 5205)
    • Florida
      • Clermont, Florida, United States, 34711
        • Clermont Oncology Center ( Site 5224)
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Hattiesburg Clinic Hematology/Oncology ( Site 5216)
    • Washington
      • Spokane, Washington, United States, 99208
        • Medical Oncology Associates, PS ( Site 5206)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nemtabrutinib
Administered daily via oral tablet.
Drug: Nemtabrutinib
65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met.
Other Names:
  • MK-1026
  • ARQ 531
Active Comparator: FCR or BR
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
25 mg/m^2 administered via intravenous (IV) infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles.
Drug: Cyclophosphamide
250 mg/m^2 administered via IV infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles.
Drug: Bendamustine
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.
Biological: Rituximab
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.
Other Names:
  • RITUXAN®/MabThera
Biological: Truxima
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.
Other Names:
  • Rituximab biosimilar
Biological: Ruxience
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.
Other Names:
  • Rituximab biosimilar
Biological: Riabni
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.
Other Names:
  • Rituximab biosimilar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR)
Time Frame: Up to approximately 49 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to approximately 94 months
OS is defined as the time from randomization to death due to any cause.
Up to approximately 94 months
Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR
Time Frame: Up to approximately 36 months
ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or Partial response (PR), per iwCLL criteria 2018 as assessed by BICR.
Up to approximately 36 months
Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR
Time Frame: Up to approximately 94 months
For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL criteria as assessed by BICR, DOR is 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.
Up to approximately 94 months
Number of Participants Who Experience an Adverse Event (AE)
Time Frame: Up to approximately 94 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 94 months
Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 94 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 94 months
Time to Next Therapy (TTNT)
Time Frame: Up to approximately 94 months
TTNT is defined as the time from randomization to initiation of the first dose of a new systemic anticancer therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or death due to any cause, whichever occurs first.
Up to approximately 94 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2023

Primary Completion (Estimated)

May 19, 2027

Study Completion (Estimated)

March 17, 2031

Study Registration Dates

First Submitted

November 14, 2022

First Submitted That Met QC Criteria

November 14, 2022

First Posted (Actual)

November 22, 2022

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1026-008
  • MK-1026-008 (Other Identifier: MSD)
  • 2021-006593-23 (EudraCT Number)
  • 2022-501481-21-00 (Registry Identifier: EU CT)
  • U1111-1274-2574 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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