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
Study ID
NCT07183878
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
12 Years - 60 Years
Healthy Volunteers
Not accepted

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.

Study Details

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.

Key Dates

Start date
Aug 20, 2025
Status verified
Sep 2025
Primary completion
Aug 20, 2027
Completion
Aug 20, 2028

Study Design

Enrollment
138 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Vene-BUCY
    Participants in this arm will receive a venetoclax-enhanced BUCY conditioning regimen before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). 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). Standard BUCY regimen includes busulfan (0.8 mg/kg every 6 hours, days -7 to -4), cyclophosphamide (60 mg/kg/day, days -3 and -2), and 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.
  • Active Comparator: BUCY
    Participants in this arm will receive the standard BUCY myeloablative conditioning regimen prior to allo-HSCT. The regimen includes busulfan (0.8 mg/kg every 6 hours, days -7 to -4), cyclophosphamide (60 mg/kg/day, days -3 and -2), and 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.

Primary Outcome Measure

Relapse-Free Survival (RFS) [ Time Frame: From the date of transplantation until relapse or death from any cause, assessed up to 24 months ]

Central Contacts

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