Resumen

El propósito de este estudio es evaluar la seguridad y eficacia de nemtabrutinib (anteriormente ARQ 531) en participantes con neoplasias hematológicas: leucemia linfocítica crónica (LLC)/linfoma linfocítico de células pequeñas (SLL), transformación de Richter, linfoma de zona marginal (MZL), linfoma de células del manto (MCL), linfoma folicular (FL) y macroglobulinemia de Waldenström (WM).

Descripción detallada

Este estudio se realizará en 2 partes: escalada y confirmación de dosis (Parte 1) y expansión de cohortes (Parte 2). Tras la determinación de la dosis recomendada de fase 2 (RP2D) en la Parte 1, el estudio prevé continuar con la Parte 2 utilizando 8 cohortes de expansión específicas por enfermedad (Cohortes A a H).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before C1D1 (the first dose of study treatment)
Has a life expectancy of at least 3 months, based on the investigator assessment
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 viral load prior to randomization
Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Has adequate organ function
Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
Participants with Human immunodeficiency virus (HIV) are eligible if they meet all of the following: the CD4 count is \>350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART
Part 1 and Part 2 (Cohorts A to C and J)
Has a confirmed diagnosis of Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) with
At least 2 lines of prior therapy (Part 1 only)
Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i. NOTE: As of Protocol Amendment 09, at least 10 CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi, BCL2i and noncovalent/reversible BTKi (all three classes of therapies are required) will be enrolled into Cohort J
Has active disease for CLL/SLL clearly documented to initiate therapy
For SLL participants in Part 2: Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
Part 2 (Cohorts D to G)
\- Has a confirmed diagnosis of and meets the following prior therapy requirements:
Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
Participants with pathologically confirmed Mantle-cell lymphoma (MCL), documented by either overexpression of cyclin D1 or t (11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
Participants with Marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to at least one prior line of systemic therapy including an anti-CD20-based regimen
Participants with Follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy and immunomodulatory agents (such as lenalidomide based regimen) (Cohort G)
Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral Computed tomography (CT) scan
Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
Part 2 (Cohort H): confirmed diagnosis of Waldenström's macroglobulinemia (WM); participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be \>15 mm in the longest diameter or \>10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival

Criterios de exclusión

Has active HBV/HCV infection (Part 1 and Part 2)
Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
Has active central nervous system (CNS) disease
Has an active infection requiring systemic therapy
Has received prior systemic anti-cancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before C1D1
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Has any clinically significant gastrointestinal abnormalities that might alter absorption
History of severe bleeding disorders

Ubicaciones

Hospital Aleman ( Site 0102)

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · +541148277000

RECRUITING

Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)

Buenos Aires, Buenos Aires F.D., Argentina

Study Coordinator · +541152990247

RECRUITING

Fundacion Estudios Clinicos ( Site 0112)

Rosario, Santa Fe Province, Argentina

Study Coordinator · +54 0341 238 4171

RECRUITING

FUNDALEU ( Site 0104)

Caba, Argentina

Study Coordinator · 5411 48771046

RECRUITING

Hospital Privado Universitario de Córdoba ( Site 0107)

Córdoba, Argentina

Study Coordinator · +541569634187

RECRUITING

Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0110)

Mendoza, Argentina

COMPLETED

Estudio de fase 2 para evaluar la eficacia y seguridad de MK-1026 en participantes con neoplasias hematológicas

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Nemtabrutinib

Ubicaciones

Hospital Aleman ( Site 0102)

Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)

Fundacion Estudios Clinicos ( Site 0112)

FUNDALEU ( Site 0104)

Hospital Privado Universitario de Córdoba ( Site 0107)

Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0110)

Patrocinadores

Contactos

Toll Free Number