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).
Recruiting now · Phase 3
Conditions studied: Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic, Small-Cell Lymphoma, Lymphoma, Small Lymphocytic, CLL, SLL
In brief
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).
Key facts
- Study ID
- NCT05947851
- Run by
- Merck Sharp & Dohme LLC
- People needed
- 735
- Starts
- 2023-08-08
- Expected to finish
- 2035-07-01
- Last updated by the study team
- 2026-08-07
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 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
You may not qualify if…
- 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
Where it is running
- IC La Serena Research ( Site 1506) — La Serena, Coquimbo Region, Chile (enrolling)
- Memorial Hospital West ( Site 5410) — Pembroke Pines, Florida, United States (enrolling)
- Fort Wayne Medical Oncology and Hematology ( Site 5444) — Fort Wayne, Indiana, United States (enrolling)
- Highlands Oncology Group ( Site 5405) — Springdale, Arkansas, United States (enrolling)
- Hattiesburg Clinic Hematology/Oncology ( Site 5416) — Hattiesburg, Mississippi, United States (enrolling)
- Oregon Health and Science University ( Site 5425) — Portland, Oregon, United States (enrolling)
- Vista Oncology ( Site 5449) — Olympia, Washington, United States (enrolling)
- Medical Oncology Associates, PS ( Site 5406) — Spokane, Washington, United States (enrolling)
- MemorialCare Health System - Long Beach Medical Center ( Site 5421) — Long Beach, California, United States (enrolling)
- Instituto Alexander Fleming ( Site 1005) — Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina (enrolling)
- Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007) — Mar del Plata, Buenos Aires, Argentina (enrolling)
- Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002) — Buenos Aires, Buenos Aires F.D., Argentina (enrolling)
- Sanatorio Parque ( Site 1003) — Rosario, Santa Fe Province, Argentina (enrolling)
- Centro Medico Fleischer ( Site 1006) — Buenos Aires, Argentina (enrolling)
- Hospital Aleman-oncohematologic diseases ( Site 1001) — Buenos Aires, Argentina (enrolling)
- Royal Adelaide Hospital ( Site 1104) — Adelaide, South Australia, Australia (enrolling)
- Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103) — Melbourne, Victoria, Australia (enrolling)
- UZ Leuven-Hematology ( Site 1200) — Leuven, Vlaams-Brabant, Belgium (enrolling)
- ZAS Cadix ( Site 1203) — Antwerp, Belgium (enrolling)
- Center for Cancer and Blood Disorders ( Site 5439) — Bethesda, Maryland, United States (enrolling)
- The Moncton Hospital ( Site 1414) — Moncton, New Brunswick, Canada (enrolling)
- Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402) — Greenfield Park, Quebec, Canada (enrolling)
- Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410) — Sherbrooke, Quebec, Canada (enrolling)
- Biocenter ( Site 1507) — Concepción, Biobio, Chile (enrolling)
- Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509) — Santiago, Region M. de Santiago, Chile (enrolling)
Full record on ClinicalTrials.gov
Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.