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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 93
- Primary Endpoint
- 1-year Relapse-Free Survival (RFS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 55 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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.
Intervention: Thiotepa (Drug)
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.
Intervention: Busulfan (BU) (Drug)
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.
Intervention: Haploidentical Peripheral Blood Stem Cell Transplantation (Procedure)
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.
Intervention: Fludarabine (Drug)
Outcomes
Primary Outcomes
1-year Relapse-Free Survival (RFS)
Time Frame: 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 Outcomes
- Overall Survival (OS)(12 months after transplantation)
- Incidence of Acute Graft-Versus-Host Disease (aGVHD)(Up to 180 days after transplantation)
- Incidence of Chronic Graft-Versus-Host Disease (cGVHD)(12 months after transplantation)
- Non-Relapse Mortality (NRM)(12 months after transplantation)
Investigators
Xianmin Song, MD
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine