Clinical trial · Interventional
Venetoclax-Enhanced BUCY vs. Standard BUCY Conditioning in High-Risk AML and MDS Patients Undergoing Allo-HSCT (Ven-BUCY Study)
A Prospective, Multicenter, Randomized Controlled Study Comparing Venetoclax-Enhanced BUCY With Standard BUCY Conditioning in High-Risk AML and MDS Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| High-Risk Acute Myeloid Leukemia | — | UNRESOLVED | — |
| High-Risk Myelodysplastic Syndromes | — | UNRESOLVED | — |
| Myelodysplastic Syndromes | Myelodysplastic Syndrome | ALIAS | 0.90 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Busulfan (BU) | Drug | Busulfan | ALIAS |
| None-placebo | Other | — | UNRESOLVED |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Vene-BUCY
- description
- Participants in this arm will receive a venetoclax-enhanced BUCY conditioning regimen before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). 1. Venetoclax is administered from day -14 to -8 (400 mg/day for patients ≥14 years; 360 mg/m²/day for patients aged 12-14 years). 2. Busulfan (0.8 mg/kg every 6 hours, days -7 to -4). 3. Cyclophosphamide (60 mg/kg/day, days -3 and -2). 4. MeCCNU (250 mg/m² on day -1). Antithymocyte globulin (ATG) may be added for donor or recipient age \>40 years. Venetoclax dose is reduced if co-administered with strong CYP3A4 inhibitors such as posaconazole.
- interventionNames
- Drug: Venetoclax
- Drug: Busulfan (BU)
- type
- ACTIVE_COMPARATOR
- label
- BUCY
- description
- Participants in this arm will receive the standard BUCY myeloablative conditioning regimen prior to allo-HSCT. 1. Busulfan (0.8 mg/kg every 6 hours, days -7 to -4). 2. Cyclophosphamide (60 mg/kg/day, days -3 and -2). 3. MeCCNU (250 mg/m² on day -1). ATG may be included in cases where the donor or recipient is over 40 years old. No venetoclax is used in this arm.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 12 Years
- Maximum age
- 60 Years
Show eligibility criteria text
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)
References
Publications (0)
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