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

NCT07025824 | Not Yet Recruiting Phase 2

• 1 other identifier: TUD-ETAL-5-084
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 4

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)

Conditions

AML - Acute Myeloid Leukemia; MDS (Myelodysplastic Syndrome)

Outcome Measures

Primary Outcomes (1)

• overall survival (OS)

  2 years after randomization

Secondary Outcomes (7)

• 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

Study Arms (2)

Treo - Arm

EXPERIMENTAL

Treo d-4 - d-2 + Flud d-6 till d-2

Drug: Treosulfan (Treo); Drug: Fludarabine (Flud)

MEL - Arm

ACTIVE COMPARATOR

Mel d-2 + Flud d-6 till d-2

Drug: Melphalan (Mel); Drug: Fludarabine (Flud)

Interventions

Treosulfan (Treo) DRUG

10 g/m2 intravenous

Treo - Arm

Melphalan (Mel) DRUG

140 mg/m2 intravenous

MEL - Arm

Fludarabine (Flud) DRUG

30 mg/m2 intravenous

MEL - Arm; Treo - Arm

Eligibility Criteria

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

You may qualify if:

• Informed consent signed by the patient capable of giving
• Patient scheduled for allogeneic transplantation within the next 3 weeks
• Age ≥ 18 years
• AML or MDS according to WHO with indication for allogeneic HCT:
• AML in first or second complete remission (CR) or complete remission with incomplete hematologic recovery (CRi/CRh) or morphologic leukemia-free state (MLFS)
• MDS according to WHO
• Increased risk for treatment-related toxicity by myeloablative conditioning according to at least one of the following criteria:
• Patients aged ≥ 50 years at transplant and/or
• HCT-CI \> 2 and/or
• AML or MDS scheduled for 2nd allogeneic HCT from different donor with minimum of 12 months after 1st allogeneic HCT
• Availability of a suitable donor:
• Matched sibling donor (MSD) or
• matched unrelated donor (MUD, 10/10 HLA) or
• 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
• haploidentical family donor

You may not qualify if:

• Patients with acute promyelocytic leukemia with t(15;17)(q22;q12)
• Patients with graft failure after previous allogeneic HCT
• Patients with scheduled 2nd allogeneic HCT within 12 months after 1st allogeneic HCT
• Pretreatment with either melphalan or treosulfan within the last 12 months prior to randomization
• Planned TBI as part of conditioning
• Severe organ dysfunction defined by either one of the following criteria:
• Serum bilirubin \> 1.5 × ULN (if not considered Gilbert-syndrome) or
• ALAT or ASAT \> 5 × ULN
• Uncontrolled infection at the time of randomization.
• 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.
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Technische Universität Dresden: lead
• medac GmbH: collaborator

Study Sites (4)

Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I

Dresden, Germany

Location

Universitätsmedizin Halle (Saale)

Halle, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik A, KMT-Zentrum

Münster, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

treosulfan; Melphalan; Honey; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Central Study Contacts

Prof. Friedrich Stölzel, MD

CONTACT

+49 431 500-22701; etal-5@ukdd.de

Desiree Kunadt, MD

CONTACT

+49 351 458 19523; etal-5@ukdd.de

Study Design

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

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-09

Locations

DE (4)