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Venetoclax-Enhanced BUCY vs. Standard BUCY Conditioning in High-Risk AML and MDS Patients Undergoing Allo-HSCT (Ven-BUCY Study)

Sponsor: First Affiliated Hospital of Zhejiang University • ClinicalTrials.gov ID: NCT07183878

Registry updated: 2026-09-02

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Description

This is a prospective, multicenter, randomized controlled trial designed to evaluate the efficacy and safety of venetoclax-enhanced BUCY (Ven-BUCY) conditioning compared to the standard BUCY regimen in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible participants aged 12 to 60 years will be randomized 1:1 to receive either Ven-BUCY or standard BUCY conditioning. The primary endpoint is relapse-free survival (RFS) at two years post-transplant. Secondary outcomes include overall survival, relapse rate, non-relapse mortality, measurable residual disease (MRD), and treatment-related adverse events. The study aims to improve post-transplant outcomes by deepening disease remission through the addition of venetoclax, a BCL-2 inhibitor known to target leukemia stem cells and enhance chemotherapy sensitivity.

Interventions

Venetoclax (Drug)
Venetoclax is administered orally at 400 mg/day for participants ≥14 years or 360 mg/m²/day for those aged 12-14 years, from day -14 to -8 before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dose is adjusted to 100 mg/day (or 90 mg/m²/day for pediatric patients) if used with strong CYP3A4 inhibitors such as posaconazole.
None-placebo (Other)
Participants in this arm will not receive venetoclax as part of their conditioning regimen. They will undergo standard myeloablative conditioning with BUCY (busulfan, cyclophosphamide, and MeCCNU), prior to allogeneic hematopoietic stem cell transplantation. This arm serves as the active comparator to evaluate the addition of venetoclax in the experimental arm.
Busulfan (BU) (Drug)
BUCY group (Control group): Busulfan (BU 0.8 mg/kg/q6h, days -7 to -4), Cyclophosphamide (CTX 60 mg/kg/day, days -3 to -2), and MeCCNU (250 mg/m²/day, day -1). For recipients or donors over 40 years of age, ATG (Thymoglobulin, total dose 2.5-4.5 mg/kg, divided over days -3 to -1) may be added.

Eligibility criteria

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)

Conditions

Acute Myeloid Leukemia High-Risk Acute Myeloid Leukemia Myelodysplastic Syndromes High-Risk Myelodysplastic Syndromes

Locations

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

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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