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)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: fludarabine and treosulfan

• Study Type: Interventional
• Enrollment (Estimated): 77
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: PAKRADOUNI Jihane; Phone Number: 0491223824; Email: pakradounij@ipc.unicancer.fr
• Study Contact Backup: Name: ARTHUR Allison; Phone Number: 0491223448; Email: arthura@ipc.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fludarabine and treosulfan; After screening and inclusion, patients will be given a RIC regimen based on the market-approved association of fludarabine and treosulfan (FT-RIC): Fludarabine (concentrate for solution for injection/infusion) is a marketed purine analogue and antineoplastic agent.; Treosulfan (powder for solution for infusion) is a marketed alkylating medication	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Progression Free Survival (PFS) defined as the time from allo-HSCT to AML relapse or death	through study completion an average of 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate adverse events related to the FT combination according to CTCAE V6.0	Conditioning related toxicity according to CTCAE V.6.0	through study completion an average of 4 years
To evaluate engraftment after FT-RIC	rate of graft failure	through study completion an average of 4 years
To evaluated hematological recovery after FT-RIC	Cumulative incidence of neutrophil and platelet recovery	after hematological recovery
to evaluate incidence of both acute and chronic GVHD after FT-RIC	Cumulative incidence of acute GVHD and Cumulative incidence of chronic GVHD	through study completion an average of 4 years
To evaluate survival, non-relapse mortality and cause of death after FT-RIC	Probability of Overall Survival and Probability of GVHD	through study completion an average of 4 years
To evaluate the immunosuppressive therapy duration after FT-RIC	Prevalence of immunosuppressive therapy (IST) and GVHD at 3, 6, 9, 12 months	through study completion an average of 4 years

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (Estimated): October 10, 2026
• Primary Completion (Estimated): October 10, 2030
• Study Completion (Estimated): February 10, 2031

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; fludarabine; treosulfan
• Other Study ID Numbers: FT-RIC-HAPLO-IPC 2025-016; 2025-523632-39-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No