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

NCT07598110 | Not Yet Recruiting Phase 2

• 2 other identifiers: FT-RIC-HAPLO-IPC 2025-0162025-523632-39-00
• Study Type: interventional
• Target: 77
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• To evaluate adverse events related to the FT combination according to CTCAE V6.0

  through study completion an average of 4 years

• To evaluate engraftment after FT-RIC

  through study completion an average of 4 years

• To evaluated hematological recovery after FT-RIC

  after hematological recovery

• to evaluate incidence of both acute and chronic GVHD after FT-RIC

  through study completion an average of 4 years

• To evaluate survival, non-relapse mortality and cause of death after FT-RIC

  through study completion an average of 4 years

Study Arms (1)

fludarabine and treosulfan

EXPERIMENTAL

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

Interventions

fludarabine and treosulfan DRUG

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

fludarabine and treosulfan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; treosulfan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

PAKRADOUNI Jihane

CONTACT

0491223824; pakradounij@ipc.unicancer.fr

ARTHUR Allison

CONTACT

0491223448; arthura@ipc.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: May 20, 2026
• Study Start (Estimated): October 10, 2026
• Primary Completion (Estimated): October 10, 2030
• Study Completion (Estimated): February 10, 2031
• Last Updated: May 20, 2026

Record last verified: 2026-05