Back to Trials
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?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

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

Memorial Hospital West ( Site 5410)

Pembroke Pines, Florida 33028

United States

Oregon Health and Science University ( Site 5425)

Portland, Oregon 97239-3011

United States

Medical Oncology Associates, PS ( Site 5406)

Spokane, Washington 99208

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

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

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

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

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

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

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

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