TBF Conditioning Regimen for Haploidentical Stem Cell Transplantation in Elderly AML Patients in First Complete Remission

Official title

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

Overview

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

• Drug Thiotepa
  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.
• Drug Busulfan (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.
• Drug Fludarabine
  Fludarabine is administered intravenously at a dose of 30 mg/m² daily from day -6 to day -2 as part of the conditioning regimen.
• Procedure Haploidentical 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.

Primary outcome measures

• 1-year Relapse-Free Survival (RFS) [Time frame: 12 months after transplantation]

Secondary outcome measures (4)

• Overall Survival (OS) [Time frame: 12 months after transplantation]
• Incidence of Acute Graft-Versus-Host Disease (aGVHD) [Time frame: Up to 180 days after transplantation]
• Incidence of Chronic Graft-Versus-Host Disease (cGVHD) [Time frame: 12 months after transplantation]
• Non-Relapse Mortality (NRM) [Time frame: 12 months after transplantation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07563920 · SHSYXY-202510-TBF-AML

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗