TBF Conditioning Regimen for Haploidentical Stem Cell Transplantation in Elderly AML Patients in First Complete Remission (TBF-AML)
A Single-Center, Prospective, Single-Arm Clinical Study Evaluating the Efficacy and Safety of Thiotepa, Busulfan, and Fludarabine (TBF) Conditioning Regimen in Haploidentical Peripheral Blood Stem Cell Transplantation for Elderly Acute Myeloid Leukemia Patients in First Complete Remission
Acute myeloid leukemia (AML) is a serious blood cancer that mainly affects older adults. For patients who achieve their first complete remission (CR1), allogeneic hematopoietic stem cell transplantation (HSCT) may provide a chance for long-term survival. However, relapse after transplantation remains a major challenge.
This study aims to evaluate the effectiveness and safety of a conditioning regimen that combines thiotepa, busulfan, and fludarabine (TBF) before haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) in elderly patients with AML in first complete remission.
Eligible patients will receive the TBF conditioning regimen followed by stem cell transplantation from a partially matched donor. Participants will be followed to assess relapse-free survival, overall survival, transplant-related complications, and infections.
The results of this study may help improve treatment strategies and outcomes for elderly AML patients undergoing transplantation.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with increasing incidence in older populations. Despite achieving first complete remission (CR1) after induction chemotherapy, elderly patients remain at high risk of relapse and have poor long-term outcomes.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered a potentially curative treatment for AML. With the development of reduced-intensity conditioning regimens and haploidentical transplantation strategies, more elderly patients are now eligible for transplantation. However, relapse after transplantation remains a major limitation.
The conditioning regimen plays a critical role in determining transplant outcomes. The combination of thiotepa, busulfan, and fludarabine (TBF) has been proposed to enhance anti-leukemic activity while maintaining acceptable toxicity. Previous retrospective and registry-based studies suggest that TBF conditioning may reduce relapse risk compared with conventional regimens, but prospective data in elderly AML patients, especially in Asian populations, remain limited.
This study is a single-center, prospective, single-arm clinical trial designed to evaluate the efficacy and safety of the TBF conditioning regimen in elderly AML patients in first complete remission undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT).
Eligible patients aged 55-75 years with AML in CR1 or CRi will receive a conditioning regimen consisting of thiotepa (day -7), busulfan (days -4 and -3), and fludarabine (days -6 to -2), followed by infusion of donor stem cells on day 0.
The primary endpoint is 1-year relapse-free survival (RFS), defined as the time from transplantation to relapse or death from any cause. Secondary endpoints include overall survival, incidence of acute and chronic graft-versus-host disease (GVHD), non-relapse mortality, hematopoietic engraftment, donor chimerism, and infection rates.
Participants will be followed regularly after transplantation with clinical assessments, laboratory tests, and bone marrow evaluations according to protocol-defined schedules.
The findings from this study are expected to provide prospective evidence for the use of TBF conditioning in elderly AML patients and support optimization of transplantation strategies in this population.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Xianmin Song, MD
- Número de teléfono: +86-13501672508
- Correo electrónico: shongxm@sjtu.edu.cn
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Age 55 to 75 years
- Diagnosed with acute myeloid leukemia (AML) based on morphology, immunophenotyping, cytogenetics, or molecular testing
- First complete remission (CR1) or complete remission with incomplete hematologic recovery (CRi)
- Eligible for haploidentical hematopoietic stem cell transplantation
- Availability of a suitable haploidentical donor
- ECOG performance status 0-2
Adequate organ function:
- Left ventricular ejection fraction ≥50%
- Oxygen saturation >92% on room air
- Serum creatinine ≤1.5 × upper limit of normal (ULN)
- Total bilirubin ≤1.5 × ULN
- AST and ALT ≤2.0 × ULN
- DLCO ≥40% and FEV1 ≥50%
- Ability to understand and sign informed consent
Exclusion Criteria:
- Secondary AML (including AML evolving from myelodysplastic syndrome or therapy-related AML)
- Active, uncontrolled infection
- Severe uncontrolled systemic disease (e.g., unstable cardiovascular disease, recent stroke, or severe organ dysfunction)
- HIV infection
- Active hepatitis B or C requiring antiviral treatment
- Pregnant or breastfeeding women
- Known hypersensitivity to study drugs
Plan de estudios
¿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)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Arms Back to Arms and Interventions * Required * § Required if Study Start Date is on or after Janu
Participants will receive a conditioning regimen consisting of thiotepa, busulfan, and fludarabine (TBF) followed by haploidentical peripheral blood stem cell transplantation.
Thiotepa is administered on day -7, busulfan on days -4 and -3, and fludarabine on days -6 to -2.
Donor stem cells are infused on day 0. Standard graft-versus-host disease prophylaxis and supportive care will be provided according to institutional guidelines.
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Thiotepa is administered intravenously at a dose of 5 mg/kg on day -7 as part of the TBF conditioning regimen prior to haploidentical peripheral blood stem cell transplantation.
Busulfan is administered intravenously at a dose of 3.2 mg/kg on days -4 and -3 as part of the TBF conditioning regimen.
Fludarabine is administered intravenously at a dose of 30 mg/m² daily from day -6 to day -2 as part of the conditioning regimen.
Haploidentical peripheral blood stem cell transplantation is performed on day 0 following conditioning.
Donor stem cells are infused, and standard graft-versus-host disease prophylaxis and supportive care are provided according to institutional protocols.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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1-year Relapse-Free Survival (RFS)
Periodo de tiempo: 12 months after transplantation
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Relapse-free survival (RFS) is defined as the time from transplantation to the first occurrence of disease relapse or death from any cause.
Patients who are alive without relapse at the last follow-up will be censored.
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12 months after transplantation
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Overall Survival (OS)
Periodo de tiempo: 12 months after transplantation
|
Overall survival is defined as the time from transplantation to death from any cause.
Patients alive at last follow-up will be censored.
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12 months after transplantation
|
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Incidence of Acute Graft-Versus-Host Disease (aGVHD)
Periodo de tiempo: Up to 180 days after transplantation
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The cumulative incidence of grade I-IV and grade III-IV acute graft-versus-host disease within 180 days after transplantation, assessed according to standard criteria.
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Up to 180 days after transplantation
|
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Incidence of Chronic Graft-Versus-Host Disease (cGVHD)
Periodo de tiempo: 12 months after transplantation
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The cumulative incidence of all-grade and moderate-to-severe chronic graft-versus-host disease, assessed according to NIH consensus criteria.
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12 months after transplantation
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Non-Relapse Mortality (NRM)
Periodo de tiempo: 12 months after transplantation
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Non-relapse mortality is defined as death without evidence of disease relapse.
Relapse is treated as a competing event.
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12 months after transplantation
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Colaboradores e Investigadores
Investigadores
- Investigador principal: Xianmin Song, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias por tipo histológico
- Enfermedades hematológicas
- Leucemia Mieloide
- Leucemia
- Enfermedades hemic y linfáticas
- Leucemia Mieloide Aguda
- Compuestos de azufre
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Hidrocarburos, acíclico
- Hidrocarburos
- Alcanos
- Alcoholes
- Butilenglicoles
- Glicolos
- Mesilatos
- Alcanosulfonatos
- Ácidos alcanosulfónicos
- Ácidos sulfónicos
- Ácidos de azufre
- Fosforamidas
- Compuestos organofosforados
- Trietilenefosforamida
- Aziridinas
- Azirines
- Busulfán
- Tiotepa
- fludarabina
Otros números de identificación del estudio
- SHSYXY-202510-TBF-AML
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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