Safety and Feasibility of a Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning before Allogeneic Stem Cell Transplantation in AML, MDS/AML and higher risk MDS (Vestal)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

29 Jan 2026 → ongoing

Decision date (initial)

2025-09-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Treatment-Related Mortality at day 28 after alloHCT

Secondary objectives 14

1. Adverse Events ≥ CTCAE grade 4 from first day of conditioning until day 28 after alloHCT:
2. Non-relapse Mortality (NRM) at day 100 after alloHCT
3. Overall survival (OS) day 100 after alloHC
4. Cumulative Incidence of Relapse (CIR) day 100 after alloHCT
5. Adverse Events ≥ CTCAE grade 3
6. Rate of delayed Engraftment at day 28 after alloHCT
7. Stage and Grade of acute GVHD at day 100 after alloHCT
8. Composite Complete Remission (cCR) Rate at day 100 after alloHCT by pathological assessement of bone marrow biopsy** and peripheral blood counts
9. Rate of MRD-negativity at day 100 after alloHCT by flow cytometric assessment
10. Rate of MRD-negativity at day 100 after alloHCT by qPCR/UHS_NGS
11. Rate of complete Donor Chimersim (based on STR using PCR) in Peripheral Blood and Bone marrow at day 100 after alloHC
12. Rate of patients with >50/µl T-helper cells at day 100 after alloHCT by flow cytometric assessment
13. Health-related Quality of Life at day 100 after alloHCT assessed with FACT-BMT4 and EQ-5D- 5L-VAS5
14. Cumulative number of hospitalized days at day 100

Conditions and MedDRA coding

Acute Myeloid Leukemia (AML), Myleodyplastic Neoplasm/Acute Myeloid Leukemia (MDS/AML) and higher risk MDS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Age between 18 and 75 years at the time of signing the Informed Consent
2. Patient is fluent in German
3. Signed written Informed Consent with the cognitive ability to understand all consequences of trial participation and to comply with all trial relatred procedures
4. Diagnosis of AML,MDS/AML (according to ICC 20226) or HR- MDS (IPSS-R7 >3.5 or IPSS-M8 >0; according to ICC 20226 and IWG 20232)
5. Myeloid neoplasm (AML, MDS/AML or higher-risk MDS according to ICC 20226 and IWG 20232) under control* at time of screening
6. Eligiblity for alloHCT according to a board of experienced haematologist
7. Karnofsky Performance Index ≥60%
8. Planned alloHCT with Peripheral Blood Stem Cells (PBS
9. nfusion of allogeneic stem cells schedulded between day 14 and day 28 after Screening
10. Availability of a suitable donor
11. Documented diffusion lung capacity for carbon monoxide (DLCO) >40% (adjusted for hemoglobin, if available) and FEV1/FVC >50%
12. Left ventricular ejection fraction (LVEF) ≥40%
13. GFR (CKD-EPI) ≥ 30 ml/min/1,73 m2
14. Bilirubin≤ 3x ULN and AST ≤ 5x ULN
15. Thoracic imaging (either X-ray or computed tomography (CT)) without evidence of active infection or second malignancy
16. Absence of an active, clinically uncontrolled infection
17. Subject (male or female) is willing to use highly effective methods during treatment and for 6 months (male or female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner1, sexual abstinence2). Female participants using homonal contraceptives should use a barrier method as well
18. Absence of pregnancy confirmed by a highly sensitive pregnancy test not older than 3 days at time of screening (only FCBP).
19. Subject agrees not to share medication

Exclusion criteria 24

1. APL (AML with t(15;17))
2. MDS/MPN (ICC 20226)
3. Karnofsky Performance Index <60%
4. Patient scheduled for haploidentical allogeneic hematopoetic stem cell transplantation or bone marrow stem cell transplantation
5. Presence of extramedullary myelosarcoma
6. Disease Relapse after prior CRc (see Appendix for Definition
7. History of allogeneic hematopoietic stem cell transplantation
8. Significant active cardiac disease within 6 months prior to the start of study treatmen
9. Documented diffusion lung capacity for carbon monoxide (DLCO) ≤40% (adjusted for hemoglobin, if available) and FEV1/FVC ≤50%
10. GFR (CKD-EPI) < 30 ml/min/1,73 m2
11. Bilirubin> 3x ULN or AST > 5x ULN
12. Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
13. Active viral infection, including hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial. An infection controlled with an approved antiviral treatment is allowed
14. Presence of Proven, Probable or Possible Invasive Fungal Disease (IFD) as defined by EORTC/MSG 20209 Definitions (please consult Appendix).
15. Serologies suggestive of recent (<6 months) infection or reactivation with/of Toxoplasma gondii (based on IgG, IgM and Avidity) or of infection with Treponema pallidum (based on TPPA).
16. Any clinically uncontrolled infection (bacterial or unknown pathogen), defined as persisting or recurring fever or rising levels of CRP (≥10 mg/dl) despite intravenous antibacterial or antifungal therapy (initiated or escalated at least 72h hours ago).
17. mmediate life‐threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation
18. Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.
19. Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at <30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed: • Basal or squamous cell carcinoma of the skin; • Carcinoma in situ of the cervix; • Carcinoma in situ of the breast; • Incidental histologic finding of prostate cancer
20. Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patients, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy)
21. Severe neurological or psychiatric disorder interfering with ability to give an informed consent
22. Women during pregnancy and lactation
23. History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
24. Participation in other trials interfering with the endpoint of this study. Prior trial participation is permitted, provided that treatment with the investigational medicinal product has been completed at least 4 days prior to screening for this trial (at least 10 days before study treatment)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS) at day 28 after alloHCT

Secondary endpoints 14

1. Adverse Events ≥ CTCAE grade 4
2. Non-relapse Mortality (NRM) at day 100 after alloHCT
3. Overall survival (OS) day 100 after alloHCT
4. Cumulative Incidence of Relapse (CIR) day 100 after alloHCT
5. Adverse Events ≥ CTCAE grade 3
6. Rate of delayed Engraftment at day 28 after alloHCT
7. Stage and Grade of acute GVHD at day 100 after alloHCT
8. Composite Complete Remission (cCR) Rate at day 100 after alloHCT by pathological assessement of bone marrow biopsy** and peripheral blood count
9. Rate of MRD-negativity at day 100 after alloHCT by flow cytometric assessment
10. Rate of MRD-negativity at day 100 after alloHCT by qPCR
11. Rate of complete Donor Chimersim
12. Rate of patients with >50/µl T-helper cells at day 100 after alloHCT by flow cytometric assessment
13. Health-related Quality of Life at day 100 after alloHCT assessed with FACT-BMT4 and EQ-5D- 5L-VAS5
14. Cumulative number of hospitalized days at day 100

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dr. Christoph Faul

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dr. Christoph Faul

Locations

1 EU/EEA country · 1 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 12 files

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

Application history

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