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

NCT07183878 | Recruiting

• 1 other identifier: Ven-BUCY
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Keywords

Venetoclax; BUCY conditioning; Allogeneic Hematopoietic Stem Cell Transplantation; Myeloablative Conditioning; Relapse-Free Survival; Graft-versus-Leukemia; GVHD; High-Risk AML; High-Risk MDS

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS)

  Relapse-Free Survival (RFS) is defined as the time from the date of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to the first documented relapse of the primary disease or death from any cause, whichever occurs first. Participants who remain alive and relapse-free will be censored at the time of last follow-up.

  From the date of transplantation until relapse or death from any cause, assessed up to 24 months

Secondary Outcomes (7)

• Overall Survival (OS)

  Up to 36 months post-transplantation

• Non-Relapse Mortality (NRM)

  Up to 36 months post-transplantation

• Relapse Rate

  Up to 36 months post-transplantation

• Measurable Residual Disease (MRD) Status

  Assessed monthly during the first 6 months, and then every 3 months until 24 months post-transplantation

• Treatment-Related Adverse Events

  From start of conditioning until 28 days after transplantation, and during follow-up up to 3 months

Study Arms (2)

Vene-BUCY

EXPERIMENTAL

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.

Drug: Venetoclax

BUCY

ACTIVE COMPARATOR

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.

Other: None-placebo

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.

Also known as: ABT-199, Venclexta

Vene-BUCY

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.

BUCY

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• /del(5q), -7, -17/abn(17p)
• Complex or monosomal karyotype

You may not qualify if:

• 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)

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Tongji Hospital: collaborator
• The Children's Hospital of Zhejiang University School of Medicine: collaborator
• Ruijin Hospital North Shanghai Jiao Tong University School of Medicine: collaborator

Study Sites (1)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Yanmin Zhao, MD

  Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School Of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanmin Zhao, MD

CONTACT

+8657187236706; yanminzhao@zju.edu.com

Zhao

CONTACT

wuhengwei@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Model Details: Participants will be stratified by disease (AML vs. MDS) and randomly assigned in a 1:1 ratio to receive either Venetoclax-enhanced BUCY conditioning or standard BUCY conditioning prior to allo-HSCT.

Study Record Dates

• First Submitted: September 14, 2025
• First Posted: September 19, 2025
• Study Start: August 20, 2025
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): August 20, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)