Evaluation of Treosulfan Versus Melphalan Conditioning Followed by PTCy in Patients With AML and MDS Undergoing Allogeneic Transplantation

Phase 2

Not yet recruiting

• Conditions: AML - Acute Myeloid Leukemia; MDS (Myelodysplastic Syndrome)
• Interventions: Drug: Treosulfan (Treo); Drug: Melphalan (Mel); Drug: Fludarabine (Flud)

• Registration Number: NCT07025824
• Lead Sponsor: Technische Universität Dresden

Brief Summary

The aim of this study is to compare the effectiveness and tolerability of two conditioning chemotherapies prior to allogeneic stem cell transplantation.

The following will also be investigated:

* Survival

* Remission and Relapse rate

* Engraftment or graft failure

* Graft versus Host Disease (GvHD)

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-10
• Study First Submitted QC: 2025-06-10
• Last Update Submitted: 2025-06-17
• Study First Posted: 2025-06-18
• Last Update Posted: 2025-06-22
• Study Start: 2025-07-15
• Primary Completion: 2028-12
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Informed consent signed by the patient capable of giving

2. Patient scheduled for allogeneic transplantation within the next 3 weeks

3. Age ≥ 18 years

4. AML or MDS according to WHO with indication for allogeneic HCT:

   1. AML in first or second complete remission (CR) or complete remission with incomplete hematologic recovery (CRi/CRh) or morphologic leukemia-free state (MLFS)
   2. MDS according to WHO

5. Increased risk for treatment-related toxicity by myeloablative conditioning according to at least one of the following criteria:

   1. Patients aged ≥ 50 years at transplant and/or
   2. HCT-CI > 2 and/or
   3. AML or MDS scheduled for 2nd allogeneic HCT from different donor with minimum of 12 months after 1st allogeneic HCT

6. Availability of a suitable donor:

   1. Matched sibling donor (MSD) or
   2. matched unrelated donor (MUD, 10/10 HLA) or
   3. mismatched unrelated donor (MMUD, single allele or antigen mismatch at HLA-A, -B, -C, or -DRB1 and no concurrent -DQB1 mismatch (9/10) shown by confirmatory typing) or
   4. haploidentical family donor

7. Planned GvHD prophylaxis with standard PTCy (with 50mg/kg body weight on days +3 and +4)

8. No history of cardiac disease that preclude allogeneic HCT and absence of active symptoms, otherwise, documented left ventricular ejection fraction

   • 40 %.

9. No need for supplementary oxygen on day of randomization

Main

Exclusion Criteria

1. Patients with acute promyelocytic leukemia with t(15;17)(q22;q12)

2. Patients with graft failure after previous allogeneic HCT

3. Patients with scheduled 2nd allogeneic HCT within 12 months after 1st allogeneic HCT

4. Pretreatment with either melphalan or treosulfan within the last 12 months prior to randomization

5. Planned TBI as part of conditioning

6. Severe organ dysfunction defined by either one of the following criteria:

   1. Serum bilirubin > 1.5 × ULN (if not considered Gilbert-syndrome) or
   2. ALAT or ASAT > 5 × ULN

7. Uncontrolled infection at the time of randomization.

8. Active viral hepatitis unless serology demonstrates clearance of infection. Occult or prior hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen and positive total hepatitis core antibodies, may be included if HBV DNA is undetectable, provided that patients are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior cured hepatitis B are eligible. Patients for hepatitis C virus (HCV) antibody are eligible provided PCR if negative for HCV RNA.

9. Pregnant or breastfeeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treo - Arm	Treosulfan (Treo)	Treo d-4 - d-2 + Flud d-6 till d-2
Treo - Arm	Fludarabine (Flud)	Treo d-4 - d-2 + Flud d-6 till d-2
MEL - Arm	Melphalan (Mel)	Mel d-2 + Flud d-6 till d-2
MEL - Arm	Fludarabine (Flud)	Mel d-2 + Flud d-6 till d-2

Primary Outcome Measures

Name	Time	Method
overall survival (OS)	2 years after randomization

Secondary Outcome Measures

Name	Time	Method
non-relapsed mortality (NRM)	2 years after randomization
relapse-free survival (RFS)	2 years after randomization
-Cumulative incidences of acute and chronic GvHD	2 years after randomization
Rates of AEs/SAEs/AESI	56 days after allogeneic stem cell transplantation
-Cumulative incidence of relapse (CIR)	2 years after randomization
-Rate of engraftment on day +28	2 years after randomization
Rate of morphologic and molecular CR/CRh/CRi/MLFS	day +56 after allogeneic stem cell transplantation

Trial Locations

Locations (4)

Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany

Universitätsmedizin Halle (Saale); 🇩🇪 Halle (Saale), Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel; 🇩🇪 Kiel, Germany

Universitätsklinikum Münster, Medizinische Klinik A, KMT-Zentrum; 🇩🇪 Münster, Germany