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NCT05947851PHASE3Recruiting

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).

Merck Sharp & Dohme LLC

Start Date

8/8/2023

Completion Date

7/1/2035

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 (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * 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 * 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 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 * 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

Interventions

DRUG

Nemtabrutinib

DRUG

Venetoclax

BIOLOGICAL

Rituximab

Interested in This Trial?

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Conditions

Leukemia, Lymphocytic, Chronic, B-CellLeukemia, Chronic LymphocyticSmall-Cell LymphomaLymphoma, Small LymphocyticCLLSLL

Locations

Highlands Oncology Group ( Site 5405)

Springdale, Arkansas 72762

United States

MemorialCare Health System - Long Beach Medical Center ( Site 5421)

Long Beach, California 90806

United States

Clermont Oncology Center ( Site 5430)

Clermont, Florida 34711

United States

Memorial Hospital West ( Site 5410)

Pembroke Pines, Florida 33028

United States

Fort Wayne Medical Oncology and Hematology ( Site 5444)

Fort Wayne, Indiana 46804

United States

Center for Cancer and Blood Disorders ( Site 5439)

Bethesda, Maryland 20817

United States

Avera Cancer Institute - Marshall ( Site 5462)

Marshall, Minnesota 56258

United States

Hattiesburg Clinic Hematology/Oncology ( Site 5416)

Hattiesburg, Mississippi 39401

United States

MidAmerica Cancer Care, LLC ( Site 5426)

Kansas City, Missouri 64132

United States

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433)

Billings, Montana 59102

United States

Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434)

Reno, Nevada 89502

United States

Atlantic Health System Morristown Medical Center ( Site 5445)

Morristown, New Jersey 07960

United States

New York Oncology Hematology, P.C. ( Site 5453)

Albany, New York 12208

United States

Oregon Health and Science University ( Site 5425)

Portland, Oregon 97239-3011

United States

Avera Cancer Institute - Aberdeen ( Site 5458)

Aberdeen, South Dakota 57401

United States

Avera Cancer Institute - Mitchell ( Site 5461)

Mitchell, South Dakota 57301

United States

Avera Cancer Institute - Pierre ( Site 5460)

Pierre, South Dakota 57501

United States

Avera Cancer Institute- Research ( Site 5437)

Sioux Falls, South Dakota 57105

United States

Avera Cancer Institute - Yankton ( Site 5459)

Yankton, South Dakota 57078

United States

PatientCare Clinical Research LLC ( Site 5435)

Sugar Land, Texas 77479

United States

University of Virginia Cancer Center ( Site 5402)

Charlottesville, Virginia 22903

United States

Vista Oncology ( Site 5449)

Olympia, Washington 98506

United States

Medical Oncology Associates, PS ( Site 5406)

Spokane, Washington 99208

United States

West Virginia University ( Site 5447)

Morgantown, West Virginia 26506

United States

University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)

Madison, Wisconsin 53792

United States

Instituto Alexander Fleming ( Site 1005)

Ciudad Autónoma de Buenos Aires, Buenos Aires C1426ANZ

Argentina

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)

Mar del Plata, Buenos Aires B7600FZO

Argentina

Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002)

Buenos Aires, Buenos Aires F.D. C1431FWO

Argentina

Sanatorio Parque ( Site 1003)

Rosario, Santa Fe Province S2000DSV

Argentina

Centro Medico Fleischer ( Site 1006)

Buenos Aires, 1414

Argentina

Hospital Aleman-oncohematologic diseases ( Site 1001)

Buenos Aires, C1118AAT

Argentina

Royal Adelaide Hospital ( Site 1104)

Adelaide, South Australia 5000

Australia

Box Hill Hospital ( Site 1106)

Box Hill, Victoria 3128

Australia

Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)

Melbourne, Victoria 3021

Australia

UZ Leuven-Hematology ( Site 1200)

Leuven, Vlaams-Brabant 3000

Belgium

ZAS Cadix ( Site 1203)

Antwerp, 2030

Belgium

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

São Paulo, 01246-000

Brazil

The Moncton Hospital ( Site 1414)

Moncton, New Brunswick E1C 6Z8

Canada

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)

Greenfield Park, Quebec J4V 2H1

Canada

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)

Sherbrooke, Quebec J1H 5H4

Canada

Biocenter ( Site 1507)

Concepción, Biobio 4070196

Chile

IC La Serena Research ( Site 1506)

La Serena, Coquimbo Region 1720430

Chile

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)

Santiago, Region M. de Santiago 7500653

Chile

FALP-UIDO ( Site 1500)

Santiago, Region M. de Santiago 7500921

Chile

Clínica Inmunocel ( Site 1511)

Santiago, Region M. de Santiago 7580206

Chile

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707)

Medellín, Antioquia 050030

Colombia

Fundación Valle del Lili ( Site 1703)

Cali, Valle del Cauca Department 760032

Colombia

Hopital Claude Huriez - CHU de Lille ( Site 2107)

Lille, Nord 59037

France

Centre Hospitalier Universitaire Estaing ( Site 2105)

Clermont-Ferrand, Puy-de-Dome 63100

France

CHD Vendee ( Site 2100)

La Roche-sur-Yon, Vendee 85925

France

Universitaetsklinikum Ulm. ( Site 2206)

Ulm, Baden-Wurttemberg 89081

Germany

Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)

Trier, Rhineland-Palatinate 54290

Germany

Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)

Leipzig, Saxony 04103

Germany

Evangelismos General Hospital of Athens ( Site 2302)

Athens, Attica 106 76

Greece

General Hospital of Athens "Laiko" ( Site 2308)

Athens, Attica 115 27

Greece

General Hospital of Athens "Laiko" ( Site 2309)

Athens, Attica 115 27

Greece

GENERAL HOSPITAL OF ALEXANDROUPOLI ( Site 2310)

Alexandroupoli, East Macedonia and Thrace 681 00

Greece

Rambam Health Care Campus ( Site 2801)

Haifa, 3109601

Israel

Hadassah Medical Center-Hemato-Oncology ( Site 2812)

Jerusalem, 9112001

Israel

Sheba Medical Center-Hemato Oncology ( Site 2809)

Ramat Gan, 5265601

Israel

Sourasky Medical Center ( Site 2811)

Tel Aviv, 6423906

Israel

Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)

Alessandria, 15121

Italy

Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)

Milan, 20132

Italy

Arcispedale Santa Maria Nuova-Hematology ( Site 2900)

Reggio Emilia, 42123

Italy

Kindai University Hospital ( Site 3005)

Sakai, Osaka 590-0197

Japan

National Hospital Organization Osaka National Hospital ( Site 3004)

Osaka, 540-0006

Japan

Centro de Infusion Superare ( Site 3314)

Mexico City, Mexico City 03100

Mexico

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

Mexico City, Mexico City 03100

Mexico

Centro de Investigacion Clinica Chapultepec ( Site 3309)

Morelia, Michoacán 58260

Mexico

Christchurch Hospital ( Site 3503)

Christchurch, Canterbury 8011

New Zealand

Palmerston North Hospital ( Site 3506)

Palmerston North, Manawatu-Wanganui 4414

New Zealand

North Shore Hospital-Department of Haematology ( Site 3505)

Auckland, 0622

New Zealand

Aotearoa Clinical Trials ( Site 3504)

Auckland, 2025

New Zealand

BRCR Global Puerto Rico - Hato Rey ( Site 3901)

San Juan, 00917

Puerto Rico

Auxilio Mutuo Cancer Center ( Site 3900)

San Juan, 00918

Puerto Rico

Alberts Cellular Therapy. ( Site 4401)

Pretoria, Gauteng 0181

South Africa

Groote Schuur Hospital ( Site 4400)

Cape Town, Western Cape 7925

South Africa

Haemalife ( Site 4407)

Kuilsriver, Western Cape 7580

South Africa

Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)

L'Hospitalet Del Llobregat, Barcelona 08908

Spain

HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)

Pozuelo de Alarcón, Madrid 28223

Spain

HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)

Valencia, Valenciana, Comunitat 46010

Spain

Tri-Service General Hospital-hematology&oncology ( Site 4703)

Taipei City, Taipei 114

Taiwan

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

Kaohsiung City, 83301

Taiwan

National Cheng Kung University Hospital ( Site 4701)

Tainan, 704

Taiwan

National Taiwan University Hospital ( Site 4704)

Taipei, 10048

Taiwan

Ege Universitesi Hastanesi ( Site 4902)

Bornova, İzmir 35100

Turkey (Türkiye)

Namik Kemal University Medical Faculty-Hematology ( Site 4912)

Tekirdağ, Tekirdas 59100

Turkey (Türkiye)

Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)

Ankara, 06100

Turkey (Türkiye)

Mega Medipol-Hematology ( Site 4904)

Istanbul, 34214

Turkey (Türkiye)

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

Istanbul, 34722

Turkey (Türkiye)

City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)

Nottingham, England NG5 1PF

United Kingdom

University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)

London-Camden, London, City of NW1 2PG

United Kingdom