Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning Before Allogeneic Stem Cell Transplantation

NCT07214064 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: VeStAL2025-521372-62-00
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

AML (Acute Myeloid Leukemia); MDS/AML; MDS (Myelodysplastic Syndrome)

Keywords

Allogeneic Stem Cell Transplantation; Venetoclax; Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning; RIC

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Primary objective of this trial is to evaluate the feasibility and safety of the augmentation of a treosulfanbased RIC regimen for alloHCT in AML, MDS/AML and HR-MDS patients with the Bcl-2-inhibitor Venetoclax. As outlined above, the aim is to increase antileukemic acitiviy without increasing morbidity and mortality in a vulnerable patient collective. This is operationalized by the following primary endpoint: 1\) Overall survival (OS) at day 28 after alloHCT Most adverse events (AEs) due to the IMPs are expected to occur before day 0. Protacted or lateonset toxicities with potentially lethal consequences cannot be ruled out. Therefore, we regard it most suitable to evaluate overall survival at day 28 after alloHCT.

  at day 28 after alloHCT

Study Arms (1)

Reduced Intensity Conditioning before Allogeneic Stem Cell Transplantation

EXPERIMENTAL

Patients with AML, MDS/AML or HR-MDS, who have either responded to remission inducing therapy or are intended for upfront transplantion receive conditioning chemotherapy as follows: IMPs: * Venetoclax 400 mg abs. day -8 to day -2 * Fludarabine 30 mg/m2 BSA day -6 to day -2 * Treosulfan 10 g/m2 BSA day -4 to day -2

Drug: RIC regimen

Interventions

RIC regimen DRUG

Venetoclax (Venclyxto®): 400 mg abs./d day -8 to -2, Fludarabine 30 mg/m2 BSA day -6 to day -2, Treosulfan 10 g/m2 BSA day -4 to day -2

Reduced Intensity Conditioning before Allogeneic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years at the time of signing the Informed Consent
• Patient is fluent in German
• Signed written Informed Consent with the cognitive ability to understand all consequences of trial participation and to comply with all trial related procedures
• Diagnosis of AML,MDS/AML (according to ICC 20226) or HRMDS (IPSS-R7 \>3.5 or IPSS-M8 \>0; according to ICC 20226 and IWG 20232)
• Myeloid neoplasm (AML, MDS/AML or HR-MDS according to ICC 20226) under control\* at time of screening, defined as one of the following:
• AML (ICC 20226):
• Scheduled for alloHCT after prior Remission
• Induction ± Consolidation:
• Achievement of at least MLFS\*\* (according to ELN 20221 criteria) after up to two cycles of intensive, anthracycline-based induction chemotherapy OR
• Achievement of at least MLFS\*\* (according to ELN 20221 criteria) after intensive, anthracycline-based induction chemotherapy folllowed by up to three cycles of cytostatic consolidation therapy OR
• Achievement of at least MLFS\*\* (according to ELN 20221) after less intensive, HMA-based treatment (up to six cycles) OR
• Achievement of at least MLFS\*\* (according to ELN 20221) after a combination of intensive and less intensive treatments (up to six cycles in total) 5.2. MDS/AML (ICC 20226):• Scheduled for alloHCT after prior Remission
• Induction ± Consolidation:
• Achievement of at least MLFS\*\* (according to ELN 20221 criteria) after up to two cycles of intensive, anthracycline-based induction chemotherapy OR
• Achievement of at least MLFS\*\* (according to ELN 20221 criteria), after intensive, anthracycline-based induction chemotherapy folllowed by up to three cycles of cytostatic consolidation therapy OR

You may not qualify if:

• APL (AML with t(15;17))
• MDS/MPN (ICC 20226)
• Karnofsky Performance Index \<60%
• Patient scheduled for haploidentical allogeneic hematopoetic stem cell transplantation or bone marrow stem cell transplantation
• Presence of extramedullary myelosarcoma
• Disease Relapse after prior CRc
• History of allogeneic hematopoietic stem cell transplantation
• Significant active cardiac disease within 6 months prior to the start of study treatment, including:
• New York Heart Association (NYHA) class III or IV congestive heart failure
• Myocardial infarction
• Unstable angina
• Cerebral apoplexy
• Severe cardiac arrhythmias
• Left ventricular ejection fraction (LVEF) \<40% by TTE
• Documented diffusion lung capacity for carbon monoxide (DLCO) ≤40% (adjusted for hemoglobin, if available) and FEV1/FVC ≤50%

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital , Department of Internal Medicine II

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

MeSH Terms

Conditions

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

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

Study Officials

• Christoph Faul, Dr.

  Sponsor's Delegate

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christoph Faul, Dr.

CONTACT

+49 7071 29-84087; Christoph.Faul@med.uni-tuebingen.de

Wolfgang Bethge, Prof. Dr.

CONTACT

+49 7071 29-83176; Wolfgang.Bethge@med.uni-tuebingen.de

Study Design

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

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 9, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)