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

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

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)

Study Overview

• Status: Not yet recruiting
• Conditions: MDS (Myelodysplastic Syndrome); AML - Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Treosulfan (Treo); Drug: Fludarabine (Flud); Drug: Melphalan (Mel)

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Prof. Friedrich Stölzel, MD; Phone Number: +49 431 500-22701; Email: etal-5@ukdd.de
• Study Contact Backup: Name: Desiree Kunadt, MD; Phone Number: +49 351 458 19523; Email: etal-5@ukdd.de

Study Locations

• Germany
  • Dresden, Germany
    • Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I
    • Principal Investigator: Desiree Kunadt, MD
  • Halle, Germany
    • Universitätsmedizin Halle (Saale)
    • Principal Investigator: Judith Schaffrath, MD
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
    • Principal Investigator: Prof. Friedrich Stölzel, MD
  • Münster, Germany
    • Universitätsklinikum Münster, Medizinische Klinik A, KMT-Zentrum
    • Principal Investigator: Matthias Stelljes, Univ.-Prof.

Participation Criteria

Eligibility Criteria

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

Description

Main 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treo - Arm; Treo d-4 - d-2 + Flud d-6 till d-2	Drug: Treosulfan (Treo); 10 g/m2 intravenous; Drug: Fludarabine (Flud); 30 mg/m2 intravenous
Active Comparator: MEL - Arm; Mel d-2 + Flud d-6 till d-2	Drug: Fludarabine (Flud); 30 mg/m2 intravenous; Drug: Melphalan (Mel); 140 mg/m2 intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival (OS)	2 years after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: medac GmbH

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 10, 2025
• First Submitted That Met QC Criteria: June 10, 2025
• First Posted (Actual): June 18, 2025

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Anemia; Leukemia; Myelodysplastic Syndromes; Anemia, Refractory; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Amino Acids, Peptides, and Proteins; Organic Chemicals; Hydrocarbons; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Amino Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Melphalan; fludarabine; Honey; treosulfan
• Other Study ID Numbers: TUD-ETAL-5-084

Drug and device information, study documents

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