Acute Myeloid Leukemia
Conditions
Keywords
Haploidentical Stem Cell Transplantation, TBF Conditioning Regimen, Thiotepa Busulfan Fludarabine, Elderly AML, Allogeneic Hematopoietic Stem Cell Transplantation, Relapse-Free Survival
Brief summary
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.
Detailed description
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.
Interventions
DRUGThiotepa
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.
DRUGBusulfan (BU)
Busulfan is administered intravenously at a dose of 3.2 mg/kg on days -4 and -3 as part of the TBF conditioning regimen.
DRUGFludarabine
Fludarabine is administered intravenously at a dose of 30 mg/m² daily from day -6 to day -2 as part of the conditioning regimen.
PROCEDUREHaploidentical Peripheral Blood Stem Cell Transplantation
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.
Sponsors
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants receive the TBF conditioning regimen followed by haploidentical peripheral blood stem cell transplantation.
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year Relapse-Free Survival (RFS) | 12 months after transplantation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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. |
| Incidence of Acute Graft-Versus-Host Disease (aGVHD) | Up to 180 days after transplantation | 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. |
| Incidence of Chronic Graft-Versus-Host Disease (cGVHD) | 12 months after transplantation | The cumulative incidence of all-grade and moderate-to-severe chronic graft-versus-host disease, assessed according to NIH consensus criteria. |
| Non-Relapse Mortality (NRM) | 12 months after transplantation | Non-relapse mortality is defined as death without evidence of disease relapse. Relapse is treated as a competing event. |
Contacts
CONTACTXianmin Song, MD
PRINCIPAL_INVESTIGATORXianmin Song
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed