Venetoclax-enhanced BUCY versus standard BUCY conditioning for high‑risk AML and MDS before allogeneic stem cell transplant

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open‑label, multicenter randomized trial will enroll 138 patients aged 12–60 with high‑risk AML or MDS and randomize them 1:1 to receive either venetoclax‑enhanced BUCY conditioning or standard BUCY prior to myeloablative allogeneic hematopoietic stem cell transplantation. The primary endpoint is relapse‑free survival at two years, and secondary endpoints include overall survival, relapse rate, non‑relapse mortality, measurable residual disease, and treatment‑related adverse events. Venetoclax, a BCL‑2 inhibitor that can deepen remissions and target leukemia stem cells, is added to standard busulfan/cyclophosphamide conditioning to test whether deeper disease clearance reduces post‑transplant relapse. Patients will be stratified by disease type (AML vs MDS) and treated across six Chinese transplant centers with protocol‑defined dosing and supportive care.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) according to 2022 WHO classification
* Age between 12 and 60 years
* High-risk MDS as defined by at least one of the following:

  * IPSS intermediate-2/high risk or IPSS-R intermediate/high/very high risk
  * TP53 mutation
  * RAS pathway mutation (e.g., NRAS, KRAS, PTPN11, CBL, NF1, RIT1, FLT3, KIT)
  * Therapy-related MDS
* High-risk AML as defined by at least one of the following:

  * TP53, RUNX1, or ASXL1 mutation
  * t(6;9)(p23;q34.1)/DEK-NUP214
  * KMT2A rearrangement
  * BCR-ABL1 fusion
  * inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)
  * -5/del(5q), -7, -17/abn(17p)
  * Complex or monosomal karyotype
  * FLT3-ITD high with wild-type NPM1
  * Initial WBC ≥ 10×10\^9/L
  * Secondary AML with history of MDS/MPN or therapy-related AML
  * AML with specific mutations (SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2)
  * MRD positive before transplantation
* For AML: must have achieved CR or CRi prior to transplantation; for MDS: bone marrow blasts \< 20%
* Availability of a matched related or unrelated donor (10/10 or 9/10 HLA match)
* ECOG performance status 0-2
* Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
* AST/ALT ≤ 3 × ULN and total bilirubin ≤ 2 × ULN
* LVEF ≥ 50% by echocardiogram
* Life expectancy \> 8 weeks
* Willingness to use effective contraception methods during and for a specified period after the study
* Signed informed consent

Exclusion Criteria:

* Uncontrolled cardiovascular disease or New York Heart Association class III/IV heart failure
* Other severe comorbid conditions that may interfere with study participation
* Known HIV infection or uncontrolled active hepatitis B or C
* Pregnant or breastfeeding women
* More than one prior hematopoietic stem cell transplantation
* Inability to understand the study protocol or provide informed consent
* History of grade ≥ 3 non-hematologic adverse reaction to prior venetoclax therapy
* Receipt of chemotherapy (except hydroxyurea/dexamethasone) or radiotherapy within 14 days before study treatment
* Ongoing use of BCR-ABL1, IDH, or FLT3 inhibitors without proper washout (≥ 7 days)

Where it's running

• The First Affiliated Hospital of Zhejiang University School of Medicine
  Hangzhou, Zhejiang, China Recruiting

Study contacts

• Principal investigator: Yanmin Zhao, MD — Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School Of Medicine
• Study coordinator: Yanmin Zhao, MD
• Email: yanminzhao@zju.edu.com
• Phone: +8657187236706

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.