Safety and Efficacy of FT14 Conditioning for Allogeneic HSCT in Acute Myeloid Leukemia

Prospective Phase II Study on Safety and Efficacy of Fludarabine Plus Treosulfan (14g) (FT14) Conditioning Regimen for Allogeneic Stem Cell Transplantation (Allo-SCT) in Acute Myeloid Leukemia (AML) Patients (≥40 <65years) (FT14-Trial)

This is a prospective, multicenter, phase II, open-label, non-randomized clinical trial designed to evaluate the safety and efficacy of the Fludarabine plus Treosulfan 14 g/m² (FT14) conditioning regimen for allogeneic stem cell transplantation (allo-SCT) in patients with Acute Myeloid Leukemia (AML) aged 40-65 years who are in complete remission.

This is a prospective, multicenter, phase II, open-label, non-randomized clinical trial designed to evaluate the safety, tolerability, and antileukemic activity of the FT14 conditioning regimen (Fludarabine plus Treosulfan 14 g/m²/day for three consecutive days) in adult patients with Acute Myeloid Leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible patients are 40 to 65 years old, in complete remission (CR), and candidates for allogeneic transplantation according to institutional criteria.

Treosulfan-based conditioning represents an effective alternative to conventional myeloablative regimens, with reduced organ toxicity and favorable immunosuppressive properties. Increasing the treosulfan dose to 14 g/m²/day aims to enhance antileukemic potency while maintaining an acceptable safety profile. Fludarabine provides additional immunosuppression and cytotoxic synergism, facilitating engraftment and disease control.

Enrolled patients will receive the FT14 conditioning regimen followed by allo-HSCT from either a matched related donor (MRD) or a matched unrelated donor (MUD). Haploidentical donors are not included in this study. Graft-versus-host disease (GVHD) prophylaxis, antimicrobial prophylaxis, and supportive care will follow each center's standard procedures.

The primary endpoint is the 1-year leukemia-free survival (LFS). Secondary endpoints include time to engraftment, cumulative incidence of graft failure, transplant-related mortality (TRM) and non-relapse mortality (NRM), relapse incidence, acute and chronic GVHD incidence and severity, overall survival (OS), and graft-versus-host disease-free, relapse-free survival (GRFS). Safety will be assessed through regimen-related toxicities, early and late post-transplant complications, and hematologic recovery kinetics.

The study is designed to provide prospective clinical evidence on the performance, tolerability, and efficacy of the FT14 regimen in adults with AML undergoing allo-HSCT, with the aim of defining its potential role as a conditioning option for this patient population.

Inclusion Criteria:

• Patients >40 <65 years of age
• Diagnosis of AML in first complete remission (CR)/complete remission with incomplete recovery (CRi)/multiflow leukemia free state (MLFS)
• Eligible for allo-SCT from HLA-identical matched related or unrelated donor as defined by molecular high-resolution typing (4 digits) at the following four HLA gene loci (HLA-A, B, C, and DRB1)
• Adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL)
• Adequate renal function (creatinine clearance ≥50 mL/min)
• ECOG Performance Status < 2
• Willing and able to comply with all of the requirements and visits in the protocol.
• Written and signed informed consent

Exclusion Criteria:

• AML patients with t(15;17); t(8;21); inv(16)
• Subject has known active CNS involvement with AML.
• Grade >2 NCI-CTCAE (v. 5) adverse events at the time of enrollment
• Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) <40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min.
• The evidence of HBV or HCV active infection (HBV DNA, HCV RNA positive test).
• Patients with HIV infection
• Current uncontrolled infections
• Patients with other life-threatening concurrent diseases
• Subjects with known hypersensitivity to any of the component medications
• Participation in another clinical trial within 1 month before the start of this trial
• Participant, both female and male, in childbearing age who do not agree to maintain an active contraceptive practice
• Pregnant or breastfeeding patients during screening