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).
Condition(s) studied
Investigational drug(s) / intervention(s)
Nemtabrutinib: 5, 20, and 45 tablets
Venetoclax: 10, 50, and 100 mg tablets
Rituximab: 100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Study 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
Primary outcome measure(s)
- Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) — Up to approximately 12 Weeks
DLT evaluation period is defined as 8 weeks after the first dose of the combination treatment of nemtabrutinib plus venetoclax Cycle 2 Day 1 in Part 1 + 4 weeks follow up. Each cycle is 4 weeks. DLTs are: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting \>7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib or venetoclax doses as a result of drug-related adverse events during the first 2 cycles; Grade 5 toxicity. - Part 1: Number of Participants Experiencing Adverse Events (AEs) — Up to approximately 28 months
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1. - Part 1: Number of Participants Discontinuing Study Treatment Due to AEs — Up to approximately 25 months
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported for Part 1. - Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Blinded Independent Central Review (BICR) — Up to approximately 71 months
PFS is defined as the time from randomization to the first documented disease progression per iwCLL criteria 2018 as accessed by BICR, or death due to any cause, whichever occurs first. PFS will be presented.
Trial sites (84)
| Facility | City | Region | Status |
|---|---|---|---|
| Highlands Oncology Group ( Site 5405) | Springdale | Arkansas | Recruiting |
| MemorialCare Health System - Long Beach Medical Center ( Site 5421) | Long Beach | California | Recruiting |
| Clermont Oncology Center ( Site 5430) | Clermont | Florida | Recruiting |
| Memorial Hospital West ( Site 5410) | Pembroke Pines | Florida | Recruiting |
| Fort Wayne Medical Oncology and Hematology ( Site 5444) | Fort Wayne | Indiana | Recruiting |
| Center for Cancer and Blood Disorders ( Site 5439) | Bethesda | Maryland | Recruiting |
| Hattiesburg Clinic Hematology/Oncology ( Site 5416) | Hattiesburg | Mississippi | Recruiting |
| MidAmerica Cancer Care, LLC ( Site 5426) | Kansas City | Missouri | Recruiting |
| Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433) | Billings | Montana | Recruiting |
| Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434) | Reno | Nevada | Recruiting |
| New York Oncology Hematology, P.C. ( Site 5453) | Albany | New York | Recruiting |
| Oregon Health and Science University ( Site 5425) | Portland | Oregon | Recruiting |
| Avera Cancer Institute- Research ( Site 5437) | Sioux Falls | South Dakota | Recruiting |
| PatientCare Clinical Research LLC ( Site 5435) | Sugar Land | Texas | Recruiting |
| University of Virginia Cancer Center ( Site 5402) | Charlottesville | Virginia | Recruiting |
| Vista Oncology ( Site 5449) | Olympia | Washington | Recruiting |
| Medical Oncology Associates, PS ( Site 5406) | Spokane | Washington | Recruiting |
| University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423) | Madison | Wisconsin | Completed |
| Instituto Alexander Fleming ( Site 1005) | Ciudad Autónoma de Buenos Aires | Buenos Aires | Recruiting |
| Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007) | Mar del Plata | Buenos Aires | Recruiting |
| Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002) | Buenos Aires | Buenos Aires F.D. | Recruiting |
| Sanatorio Parque ( Site 1003) | Rosario | Santa Fe Province | Recruiting |
| Centro Medico Fleischer ( Site 1006) | Buenos Aires | Argentina | Recruiting |
| Hospital Aleman-oncohematologic diseases ( Site 1001) | Buenos Aires | Argentina | Recruiting |
| Royal Adelaide Hospital ( Site 1104) | Adelaide | South Australia | Recruiting |
| Box Hill Hospital ( Site 1106) | Box Hill | Victoria | Recruiting |
| Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103) | Melbourne | Victoria | Recruiting |
| UZ Leuven-Hematology ( Site 1200) | Leuven | Vlaams-Brabant | Recruiting |
| ZAS Cadix ( Site 1203) | Antwerp | Belgium | Recruiting |
| ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308) | São Paulo | Brazil | Active Not Recruiting |
| The Moncton Hospital ( Site 1414) | Moncton | New Brunswick | Recruiting |
| Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402) | Greenfield Park | Quebec | Recruiting |
| Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410) | Sherbrooke | Quebec | Recruiting |
| Biocenter ( Site 1507) | Concepción | Biobio | Recruiting |
| IC La Serena Research ( Site 1506) | La Serena | Coquimbo Region | Recruiting |
| Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509) | Santiago | Region M. de Santiago | Recruiting |
| FALP-UIDO ( Site 1500) | Santiago | Region M. de Santiago | Recruiting |
| Clínica Inmunocel ( Site 1511) | Santiago | Region M. de Santiago | Recruiting |
| Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707) | Medellín | Antioquia | Recruiting |
| Fundación Valle del Lili ( Site 1703) | Cali | Valle del Cauca Department | Recruiting |
+ 44 more sites — see the full list on the official registry below.
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT05947851 on ClinicalTrials.gov ↗ ← All trials in Italy