1026-010 - 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)

Studio Clinico

Patologia: Linfomi, Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

- 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, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 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.

Criteri di esclusione: 

- 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 3 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.
- Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
- 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) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
- 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.

Trattamento sperimentale: 

Nemtabrutinib + Venetoclax

Trattamento di controllo: 

Venetoclax + Rituximab

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-501560-17-00

Data di inserimento: 09.07.2024

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na