Randomized Evaluation of Treosulfan versus Melphalan conditioning fol-lowed by PTCY in Patients with AML and MDS undergoing allogeneic Transplantation (RELEVANT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technische Universitat Dresden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Jan 2026 → ongoing

Decision date (initial)

2025-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

medac GmbH

External identifiers

EU CT number

2023-507879-21-00

ClinicalTrials.gov

NCT07025824

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate efficacy of fludarabine plus either treosulfan or melphalan in allogeneic HCT with PTCy-based GvHD prophylaxis in patients with AML in 1st or 2nd CR or patients with MDS.

Secondary objectives 5

1. To evaluate the rate of remission in both treatment arms.
2. To evaluate the engraftment and graft failure in both treatment arms.
3. To evaluate the GvHD (acute and chronic) in both treatment arms.
4. To Evaluate the survival and non-relapse mortality in both treatment arms.
5. To evaluate the tolerability in both treatment arms.

Conditions and MedDRA coding

AML and MDS undergoing allogeneic Transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signed informed consent form by patient
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: a) AML in first or second complete remission (CR) or complete remission with incomplete hematologic recovery (CRi/CRh) or morphologic leukemia-free state (MLFS) b) MDS according to WHO
5. Increased risk for treatment-related toxicity by myeloablative conditioning according to at least one of the following criteria: a) Patients aged ≥ 50 years at transplant and/or b) HCT-CI > 2 and/or c) 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: a) Matched sibling donor (MSD) or b) Matched unrelated donor (MUD, 10/10 HLA) or c) 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 d) 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 precludes allogeneic HCT and absence of active symptoms, otherwise, documented left ventricular ejection fraction ≥ 40 %
9. No need for supplementary oxygen on day of randomization
10. Men must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 6 months after the last dose of study drug
11. Women must fulfil at least one of the following criteria in order to be eligible for trial inclusion: a) post-menopausal (12 months of natural amenorrhoea or 6 months of amenorrhoea with serum FSH > 40 U/ml) b) postoperative (i.e.6 weeks) after bilateral ovariectomy with or without hysterectomy) c) Women of childbearing potential must have a negative serum pregnancy test performed within 7 days before the first dose of study drug d) continuous and correct application of a contraceptive method with an Pearl Index < 1% per year (e.g. implants, depots, oral contraceptives, intrauterine device – IUD) from time point of signing the informed consent until 6 months after the last dose of study drug e) sexual abstinence from time point of signing the informed consent until 6 months after the last dose of study drug f) Vasectomy of the sexual partner

Exclusion criteria 13

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: a) Serum bilirubin > 1.5 × ULN (if not considered Gilbert-syndrome) or b) ASAT 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. Hypersensitivity known from medical history to one of the drugs used or their ingredients or to drugs with a similar chemical structure
10. Addictions or other illnesses that do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences
11. Pregnant or breastfeeding women
12. Having received any unlicensed drug within 30 days or 5 half-lives, whichever is greater, prior to randomization
13. Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) as time-to-event endpoint

Secondary endpoints 7

1. ­non-relapse mortality (NRM)
2. ­Graft-versus-host-free and relapse-free survival (GRFS)
3. ­Cumulative incidences of acute and chronic GvHD (NIH criteria)
4. ­Rates of AEs/SAEs/AESI
5. ­Cumulative incidence of relapse (CIR) and Relapse-free survival (RFS)
6. ­Rate of morphologic and molecular CR/CRh/CRi/MLFS
7. ­Rate of engraftment on day +28 and Rate of complete donor-type chimerism on day +28 and day +56

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technische Universitat Dresden

Sponsor organisation

Technische Universitat Dresden

Address

Mommsenstrasse 11, Raecknitz/zschertnitz Raecknitz/zschertnitz

City

Dresden

Postcode

01069

Country

Germany

Scientific contact point

Organisation

Technische Universitat Dresden

Contact name

Prof. Dr. med. Friedrich Stölzel

Public contact point

Organisation

Technische Universitat Dresden

Contact name

Prof. Dr. med. Friedrich Stölzel

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications