Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML
15 de septiembre de 2026 actualizado por: Institute of Hematology & Blood Diseases Hospital, China
A Phase Ib Study of Liposomal Mitoxantrone Combined With Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit Patients With Acute Myeloid Leukemia
This prospective, open-label, multicenter phase Ib trial will evaluate the safety, tolerability, and RP2D of the VAM regimen (liposomal mitoxantrone + azacitidine [AZA] + venetoclax [VEN]) in elderly or unfit patients with newly diagnosed AML. A standard 3+3 dose escalation will enroll 12-30 patients, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed.
Induction therapy will consist of up to two 28-day cycles. Responders achieving CR/CRi/MLFS will be eligible for up to 4 consolidation cycles (total ≤6 cycles), after which they will proceed to maintenance with either AZA+VEN or observation.
Descripción general del estudio
Estado
Estado
Aún no reclutando
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Intervencionista
Inscripción (Estimado)
Inscripción
30
Fase
Fase
- Fase 1
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
Inclusion Criteria:
Subjects eligible for enrollment in this study must meet all of the following criteria:
- Diagnosis of acute myeloid leukemia (AML) according to the WHO 2022 or ICC criteria, excluding acute promyelocytic leukemia (APL).
- No prior therapy for AML, except hydroxyurea for the management of hyperleukocytosis.
Meeting at least one of the following criteria:
- Age ≥ 75 years;
- Age 18-74 years with at least one of the following conditions precluding suitability for intensive chemotherapy:
i. ECOG performance status 2-3; ii. Cardiac dysfunction with left ventricular ejection fraction (LVEF) ≤ 50%; iii. Pulmonary dysfunction with diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; iv. Creatinine clearance 30-45 mL/min; v. Other major organ dysfunction or comorbidities that, in the investigator's judgment, render the patient unsuitable for intensive chemotherapy.
- ECOG performance status 0-3.
- Life expectancy ≥ 3 months.
- Patients of childbearing potential agree to use effective contraception during the treatment period and for at least 6 months after the last dose of study treatment.
- Voluntary written informed consent provided.
Exclusion Criteria:
Subjects who meet any of the following criteria will not be eligible for enrollment in this study:
- Acute promyelocytic leukemia (APL)..
- Active central nervous system (CNS) leukemia.
- Prior targeted therapy or chemotherapy for AML, excluding hydroxyurea.
- Uncontrolled active infection.
- Uncontrolled cardiovascular disease: New York Heart Association (NYHA) class III-IV heart failure, myocardial infarction or unstable angina within 6 months before enrollment, or uncontrolled hypertension.
- Left ventricular ejection fraction (LVEF) < 40%.
- Concurrent active malignancy, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer.
- Known hypersensitivity to the study drugs or their excipients.
- Pregnant or breastfeeding women.
- Any other condition that, in the investigator's judgment, would make the patient unsuitable for study participation.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
1
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Experimental: Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen
The trial will employ a standard 3+3 dose escalation design, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed. Venetoclax duration will be sequentially escalated (9 vs. 14 days), choosing the longest duration without dose-limiting toxicity (DLT) in 3-6 evaluable patients. The RP2D for liposomal mitoxantrone is the highest dose with ≤1 DLT in 6 patients; if DL4 is tolerated, RP2D = 20 mg/m² on day 1. |
Liposome Mitoxantrone: 8, 12, 16, and 20 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks
Venetoclax(9 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po), every 4 weeks Venetoclax(14 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7, every 4 weeks
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Dose-Limiting Toxicity (DLT)
Periodo de tiempo: Cycle 1(up to 42 days)
|
To evaluate the safety, tolerability, and RP2D of the VAM regimen in newly diagnosed elderly/unfit AML patients.
|
Cycle 1(up to 42 days)
|
|
Incidence of treatment-related adverse events
Periodo de tiempo: From day 1 of treatment to 28 days after the last dose
|
The safety of the drug was evaluated by NCI-CTC AE 5.0 standard which including hematologic and non-hematologic toxicity
|
From day 1 of treatment to 28 days after the last dose
|
|
Composite complete remission (CRc) rate
Periodo de tiempo: Up to approximately eight weeks
|
Proportion of patients with complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia-free state (MLFS)
|
Up to approximately eight weeks
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Complete remission (CR) rate
Periodo de tiempo: Up to approximately eight weeks
|
Proportion of patients with complete remission (CR)
|
Up to approximately eight weeks
|
|
Complete remission with incomplete hematologic recovery (CRi) rate
Periodo de tiempo: Up to approximately eight weeks
|
Proportion of patients with complete remission with incomplete hematologic recovery (CRi)
|
Up to approximately eight weeks
|
|
Morphologic leukemia-free state (MLFS) rate
Periodo de tiempo: Up to approximately eight weeks
|
Proportion of patients with morphologic leukemia-free state (MLFS)
|
Up to approximately eight weeks
|
|
Event-free survival (EFS)
Periodo de tiempo: Up to approximately 5 years
|
It is defined as the time from the start of study treatment to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first)
|
Up to approximately 5 years
|
|
Overall survival (OS)
Periodo de tiempo: Up to approximately 5 years
|
It is defined as the time from the start of study treatment to the death from any cause
|
Up to approximately 5 years
|
|
Relapse-free Survival (RFS)
Periodo de tiempo: Up to approximately 5 years
|
It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up
|
Up to approximately 5 years
|
|
Duration of Response (DoR)
Periodo de tiempo: Up to approximately 5 years
|
It is defined as the time from the first documentation of CRc to relapse
|
Up to approximately 5 years
|
|
30-day postinduction mortality
Periodo de tiempo: Up to approximately 30 days
|
It is defined as death from any cause within 30 days after the start of induction
|
Up to approximately 30 days
|
|
60-day postinduction mortality
Periodo de tiempo: Up to approximately 60 days
|
t is defined as death from any cause within 60 days after the start of induction
|
Up to approximately 60 days
|
|
Measurable Residual Disease (MRD) negative rate by flow cytometry
Periodo de tiempo: Up to approximately eight weeks
|
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by flow cytometry
|
Up to approximately eight weeks
|
|
Measurable Residual Disease (MRD) negative rate by molecular testing
Periodo de tiempo: Up to approximately eight weeks
|
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by molecular testing
|
Up to approximately eight weeks
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
30 de octubre de 2026
Finalización primaria (Estimado)
Finalización primaria
31 de diciembre de 2027
Finalización del estudio (Estimado)
Finalización del estudio
31 de diciembre de 2032
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
15 de septiembre de 2026
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
15 de septiembre de 2026
Publicado por primera vez (Actual)
Publicado por primera vez
18 de septiembre de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
18 de septiembre de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
15 de septiembre de 2026
Última verificación
Última verificación
1 de agosto de 2026
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
- venetoclax
Otros números de identificación del estudio
Otros números de identificación del estudio
- IIT2026104
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .