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).

Официальное название

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)

Обзор

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).

Вмешательства

• Препарат Nemtabrutinib
  5, 20, and 45 tablets
• Препарат Venetoclax
  10, 50, and 100 mg tablets
• Биопрепарат Rituximab
  100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion

Первичные конечные точки

• Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [Срок оценки: Up to approximately 12 Weeks]
• Part 1: Number of Participants Experiencing Adverse Events (AEs) [Срок оценки: Up to approximately 28 months]
• Part 1: Number of Participants Discontinuing Study Treatment Due to AEs [Срок оценки: 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) [Срок оценки: Up to approximately 71 months]

Вторичные конечные точки (6)

• Part 2: Undetectable Minimal Residual Disease (MRD) Rate in Bone Marrow as Assessed by Central Laboratory [Срок оценки: Up to approximately 46 months]
• Part 2: Overall Survival (OS) [Срок оценки: Up to approximately 108 months]
• Part 2: Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR [Срок оценки: Up to approximately 71 months]
• Part 2: Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR [Срок оценки: Up to approximately 108 months]
• Part 2: Number of Participants Experiencing AEs [Срок оценки: Up to approximately 28 months]
• Part 2: Number of Participants Discontinuing Study Treatment Due to AEs [Срок оценки: Up to approximately 25 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Highlands Oncology Group ( Site 5405) — Springdale
• MemorialCare Health System - Long Beach Medical Center ( Site 5421) — Long Beach
• Memorial Hospital West ( Site 5410) — Pembroke Pines
• Fort Wayne Medical Oncology and Hematology ( Site 5444) — Fort Wayne
• Center for Cancer and Blood Disorders ( Site 5439) — Bethesda
• Hattiesburg Clinic Hematology/Oncology ( Site 5416) — Hattiesburg
• Oregon Health and Science University ( Site 5425) — Portland
• Vista Oncology ( Site 5449) — Olympia
• … и ещё 2 центра

Аргентина · 6 центров

• Instituto Alexander Fleming ( Site 1005) — Ciudad Autónoma de Buenos Aires
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007) — Mar del Plata
• Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002) — Buenos Aires
• Sanatorio Parque ( Site 1003) — Rosario
• Centro Medico Fleischer ( Site 1006) — Buenos Aires
• Hospital Aleman-oncohematologic diseases ( Site 1001) — Buenos Aires

Чили · 5 центров

• Biocenter ( Site 1507) — Concepción
• IC La Serena Research ( Site 1506) — La Serena
• Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509) — Santiago
• FALP-UIDO ( Site 1500) — Santiago
• Clínica Inmunocel ( Site 1511) — Santiago

Turkey (Türkiye) · 5 центров

• Ege Universitesi Hastanesi ( Site 4902) — Bornova
• Namik Kemal University Medical Faculty-Hematology ( Site 4912) — Tekirdağ
• Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913) — Ankara
• Mega Medipol-Hematology ( Site 4904) — Istanbul
• TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906) — Istanbul

Израиль · 4 центра

• Rambam Health Care Campus ( Site 2801) — Haifa
• Hadassah Medical Center-Hemato-Oncology ( Site 2812) — Jerusalem
• Sheba Medical Center-Hemato Oncology ( Site 2809) — Ramat Gan
• Sourasky Medical Center ( Site 2811) — Tel Aviv

Канада · 3 центра

• The Moncton Hospital ( Site 1414) — Moncton
• Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402) — Greenfield Park
• Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospital — Sherbrooke

Франция · 3 центра

• Hopital Claude Huriez - CHU de Lille ( Site 2107) — Lille
• Centre Hospitalier Universitaire Estaing ( Site 2105) — Clermont-Ferrand
• CHD Vendee ( Site 2100) — La Roche-sur-Yon

Италия · 3 центра

• Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906) — Alessandria
• Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902) — Milan
• Arcispedale Santa Maria Nuova-Hematology ( Site 2900) — Reggio Emilia

Мексика · 3 центра

• Centro de Infusion Superare ( Site 3314) — Mexico City
• Health Pharma Professional Research S.A. de C.V: ( Site 3301) — Mexico City
• Centro de Investigacion Clinica Chapultepec ( Site 3309) — Morelia

ЮАР · 3 центра

• Alberts Cellular Therapy. ( Site 4401) — Pretoria
• Groote Schuur Hospital ( Site 4400) — Cape Town
• Haemalife ( Site 4407) — Kuilsriver

Испания · 3 центра

• Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 46 — L'Hospitalet Del Llobregat
• HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602) — Pozuelo de Alarcón
• HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603) — Valencia

Австралия · 2 центра

• Royal Adelaide Hospital ( Site 1104) — Adelaide
• Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103) — Melbourne

Бельгия · 2 центра

• UZ Leuven-Hematology ( Site 1200) — Leuven
• ZAS Cadix ( Site 1203) — Antwerp

Германия · 2 центра

• Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203) — Trier
• Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201 — Leipzig

Великобритания · 2 центра

• City Hospital, Nottingham University Hospitals-Hematology ( Site 5002) — Nottingham
• University College London Hospital-Cancer Clinical Trials Unit ( Site 5001) — London-Camden

Бразилия · 1 центр

• ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308) — São Paulo

Колумбия · 1 центр

• Fundación Valle del Lili ( Site 1703) — Cali

Пуэрто-Рико · 1 центр

• Auxilio Mutuo Cancer Center ( Site 3900) — San Juan

Идентификаторы

NCT: NCT05947851 · 1026-010 · MK-1026-010 · BELLWAVE-010 · 2022-501560-17-00 · U1111-1281-1520 · jRCT2061260028

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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