Lisaftoclax Plus Azacitidine Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse
Maintenance Therapy With Lisaftoclax Plus Azacitidine After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse: A Multicenter, Open-Label, Randomized Controlled Trial
This study evaluates the efficacy and safety of maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with acute myeloid leukemia (AML) at high risk of relapse.
The main questions this study aims to answer are:
- Does maintenance therapy with lisaftoclax plus azacitidine improve disease-free survival compared with observation alone after allo-HSCT?
- Does maintenance therapy reduce relapse and improve overall survival?
- What adverse events and safety outcomes are associated with this treatment strategy?
Researchers will compare maintenance therapy with lisaftoclax plus azacitidine with observation or best supportive care in patients with AML at high risk of relapse following allo-HSCT.
Participants will:
- Be randomly assigned in a 2:1 ratio to receive either maintenance therapy with lisaftoclax plus azacitidine or observation.
- Receive study treatment for up to 12 cycles or undergo observation according to the study assignment.
- Undergo regular follow-up assessments, disease monitoring, and safety evaluations after transplantation.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 3
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment in this study:
- Diagnosed with acute myeloid leukemia (AML), excluding acute promyelocytic leukemia, according to the WHO 2022 classification, and without FLT3-ITD or FLT3-TKD mutations.
- Presence of at least one of the following high-risk features:
1) Adverse-risk AML according to the ELN 2022 risk classification; 2) Refractory AML; 3) Relapsed AML; 4) Persistent measurable residual disease positivity prior to transplantation; 5) Secondary AML transformed from myelodysplastic syndrome or myeloproliferative neoplasm.
3. Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT).
4. Stable hematologic recovery, defined as: Absolute neutrophil count ≥ 1.0 × 10⁹/L without G-CSF support; and Platelet count ≥ 50 × 10⁹/L without platelet transfusion within 7 days prior to randomization.
5. Age ≥18 years and ≤75 years. 6. Eastern Cooperative Oncology Group performance status of 0-2. 7. Ability to provide written informed consent before initiation of any study procedures.
8. Written informed consent may be provided by the participant or an authorized immediate family member in accordance with local regulations.
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded from the study:
- Evidence of disease relapse or impending relapse prior to randomization after transplantation, as determined by morphologic assessment or flow cytometry.
- Active or uncontrolled acute graft-versus-host disease (aGVHD) requiring systemic immunosuppressive therapy.
- Uncontrolled active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 7 days prior to enrollment.
- Moderate or severe hepatic impairment, as defined by the Child-Pugh classification.
- Severe renal impairment, defined as creatinine clearance <30 mL/min (calculated using the Cockcroft-Gault formula) or requirement for dialysis.
- Pregnancy, or unwillingness/inability to use adequate contraception during the study treatment period.
- Psychiatric disorders or other medical conditions that, in the investigator's judgment, would interfere with compliance with study treatment, monitoring, or study procedures.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Sin intervención: Observación
|
|
|
Experimental: Lisaftoclax plus Azacitidine Maintenance Therapy
|
Participants will receive maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Lisaftoclax will be administered orally at a dose of 400 mg once daily on Days 1-7 of each treatment cycle.
Azacitidine will be administered at a dose of 32 mg/m² by subcutaneous injection or intravenous infusion on Days 1-5 of each treatment cycle.
Each treatment cycle is 28 days in length.
Maintenance therapy will be administered for up to 12 cycles or until 15 months after allo-HSCT, whichever occurs first.
The dose of lisaftoclax may be modified according to concomitant medications and treatment-related hematologic toxicities.
The interval between treatment cycles may be extended based on individual tolerability and hematologic recovery.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Disease-Free Survival
Periodo de tiempo: 2 years
|
Disease status (including relapse) and survival outcomes will be evaluated for the assessment of disease-free survival (DFS).
DFS is defined as the time from randomization to the first occurrence of relapse or death from any cause.
Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status (MRD-positive vs. MRD-negative) to assess the consistency of treatment effects across MRD subgroups.
|
2 years
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cumulative Incidence of Relapse
Periodo de tiempo: 2 years
|
The cumulative incidence of relapse will be assessed during the follow-up period.
|
2 years
|
|
Overall Survival
Periodo de tiempo: 2 years.
|
Overall survival (OS) is defined as the time from randomization to death from any cause.
Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status to assess the consistency of treatment effects between MRD-positive and MRD-negative patients.
|
2 years.
|
|
Cumulative Incidence of Pre-emptive Therapy.
Periodo de tiempo: 2 years
|
Pre-emptive therapy rate is defined as the proportion of patients who receive additional anti-leukemic treatment triggered by measurable residual disease positivity or other molecular evidence of impending relapse after allogeneic hematopoietic stem cell transplantation.
|
2 years
|
|
Cumulative Incidence of Non-Relapse Mortality
Periodo de tiempo: 2-years.
|
Non-relapse mortality, defined as death without prior disease relapse or progression, assessed as a cumulative incidence.
|
2-years.
|
|
Treatment-Related Adverse Events
Periodo de tiempo: From initiation of maintenance therapy to 30 days after last dose of study drug.
|
Incidence, severity, and type of adverse events will be evaluated and graded according to CTCAE v5.0 during maintenance therapy and follow-up.
|
From initiation of maintenance therapy to 30 days after last dose of study drug.
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias por tipo histológico
- Enfermedades hematológicas
- Leucemia Mieloide
- Leucemia
- Enfermedades hemic y linfáticas
- Leucemia Mieloide Aguda
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Ácidos nucleicos, nucleótidos y nucleósidos
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Compuestos AZA
- Nucleósidos
- Ribonucleósidos
- Azacitidina
- LisActoclax
Otros números de identificación del estudio
Otros números de identificación del estudio
- IIT2026015
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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