Resumen

El propósito de este estudio es evaluar la seguridad y tolerabilidad, y confirmar la dosis de nemtabrutinib en combinación con venetoclax en participantes con LLC/LLP en recaída o refractaria (R/R). Las hipótesis primarias del estudio son que la combinación de nemtabrutinib más venetoclax es superior a venetoclax más rituximab (VR) con respecto a la supervivencia libre de progresión (SLP) según los criterios del Taller Internacional sobre Leucemia Linfítica Crónica (iwCLL) de 2018, evaluada por una revisión central independiente cegada (RCIC).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Ubicaciones

Instituto Alexander Fleming ( Site 1005)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · +541132218900

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)

Mar del Plata, Buenos Aires, Argentina

Study Coordinator · +542234963224

RECRUITING

Sanatorio Parque ( Site 1003)

Rosario, Santa Fe Province, Argentina

Study Coordinator · +543414200222

RECRUITING

Centro Medico Fleischer ( Site 1006)

Buenos Aires, Argentina

Study Coordinator · +541148544097

RECRUITING

Hospital Aleman-oncohematologic diseases ( Site 1001)

Buenos Aires, Argentina

Study Coordinator · +541148277000

RECRUITING

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Nemtabrutinib

Venetoclax

Rituximab

Ubicaciones

Instituto Alexander Fleming ( Site 1005)

Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)

Sanatorio Parque ( Site 1003)

Centro Medico Fleischer ( Site 1006)

Hospital Aleman-oncohematologic diseases ( Site 1001)

Patrocinadores

Contactos

Toll Free Number