FLUDARABINE-TREOSULFAN REDUCED INTENSITY CONDITIONING REGIMEN PRIOR HAPLOIDENTICAL STEM CELL TRANSPLANTATION WITH POST TRANSPLANTATION CYCLOPHOSPHAMIDE FOR OLDER AND/OR FRAIL PATIENTS WITH AML

Official title

FLUDARABINE-TREOSULFAN REDUCED INTENSITY CONDITIONING REGIMEN PRIOR HAPLOIDENTICAL STEM CELL TRANSPLANTATION WITH POST TRANSPLANTATION CYCLOPHOSPHAMIDE FOR OLDER AND/OR FRAIL PATIENTS WITH AML: FT-RIC-HAPLO-IPC 2025-016

Overview

Acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) predominantly affect older adults, and their incidence continues to rise with advanced age. For many patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option capable of providing long-term disease control through the graft-versus-leukemia (GVL) effect. Historically, however, allo-HSCT was rarely offered to patients older than 50 years because of the high morbidity and mortality associated with myeloablative conditioning regimens and limited supportive care strategies. Over the past two decades, advances in reduced-intensity conditioning (RIC), infection prophylaxis, and donor availability have profoundly transformed the landscape, allowing increasing numbers of older patients to access transplantation. Multiple studies have demonstrated that allo-HSCT confers a survival benefit in older AML patients in complete remission compared with consolidation chemotherapy alone. The intensity of conditioning profoundly influences both relapse risk and non-relapse mortality (NRM). myeloablative conditioning (NMAC) regimens are attractive for older adults due to their low toxicity but rely solely on the immunologic GVL effect and thus carry a higher relapse risk. Reduced-intensity conditioning (RIC) regimens, incorporating intermediate-dose alkylating agents such as busulfan, melphalan, or thiotepa, offer stronger anti-leukemic effect but at the cost of greater toxicity. These observations underscore the central question: can a conditioning regimen combine strong anti-leukemic potency with the low toxicity required for older patients undergoing Haplo-SCT? The main objective is to evaluate the efficacy of FT-RIC regimen before Haplo-SCT for older and/or frail patients diagnosed with AML, who are not eligible for a myeloablative conditioning (MAC) regimen. To achieve this objective, the investigators will assess Progression Free Survival (PFS) defined as the time from allo-HSCT to AML relapse or death. This is a Multicenter trial, single arm prospective of phase II. Once the conditioning has been administered and the transplant performed, the patient will receive standard routine follow-up care, with the addition of questionnaires, and for patients followed at the Institut Paoli Calmettes only, blood samples will be collected.

Interventions

• Drug fludarabine and treosulfan
  As per standard practices, patients will be hospitalized during the treatment period. The treatment is administered by the nurses of the department under the responsibility of the investigator.Fludarabine (30 mg/m²/day from day-6 to day-2), iv andTreosulfan (10 g/m²/day from day-4 to day-2), iv

Primary outcome measures

• The main objective is to evaluate the efficacy of FT-RIC regimen before Haplo-SCT for older and/or frail patients diagnosed with AML, who are not eligible for a MAC regimen. [Time frame: through study completion an average of 4 years]

Secondary outcome measures (6)

• To evaluate adverse events related to the FT combination according to CTCAE V6.0 [Time frame: through study completion an average of 4 years]
• To evaluate engraftment after FT-RIC [Time frame: through study completion an average of 4 years]
• To evaluated hematological recovery after FT-RIC [Time frame: after hematological recovery]
• to evaluate incidence of both acute and chronic GVHD after FT-RIC [Time frame: through study completion an average of 4 years]
• To evaluate survival, non-relapse mortality and cause of death after FT-RIC [Time frame: through study completion an average of 4 years]
• To evaluate the immunosuppressive therapy duration after FT-RIC [Time frame: through study completion an average of 4 years]

Eligibility criteria

Inclusion criteria

• Patient with age between 60 and 75 years old ; or aged 18-59 years if considered by the investigator for any reason as ineligible for MAC regimen (as defined by the EBMT criteria17), notably in case of HCT-CI ≥ 3 (patients planned by the investigators to receive a RIC regimen in clinical routine practice);
• Patients with AML according to the ELN2022 classification criteria requiring allo-HSCT including the MDS/AML sub category);
• Less than 5% bone marrow blast at the time of inclusion (i.e. CR, CRi, CRh, or MLFS after prior treatment, according to ELN 2022);
• Allo-HSCT planed with a haploidentical donor;
• Covered by a Healthcare System;
• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements.

Exclusion criteria

• Left ventricular function < 40% ;
• Renal clearance < 50 mL/min ;
• Any severe uncontrolled medical condition considered by the investigator as a contraindication for using treosulfan;
• Pregnant women or those who may become pregnant (without effective contraception) or breastfeeding;
• Adults under legal protection (guardianship, curatorship, or judicial protection);
• Inability to comply with the medical follow-up of the trial for geographical, social, or psychological reasons.

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: NCT07598110 · FT-RIC-HAPLO-IPC 2025-016 · 2025-523632-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗