Venetoclax-enhanced BUCY versus standard BUCY conditioning for high‑risk AML and MDS before allogeneic stem cell transplant
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
This will test whether adding venetoclax to BUCY conditioning before allogeneic stem cell transplant helps patients aged 12–60 with high‑risk AML or MDS stay in remission longer.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 138 (estimated) |
| Ages | 12 Years to 60 Years |
| Sex | All |
| Sponsor | First Affiliated Hospital of Zhejiang University Academic / other |
| Drugs / interventions | chemotherapy, cyclophosphamide |
| Locations | 1 site (Hangzhou, Zhejiang) |
| Trial ID | NCT07183878 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates are patients aged 12–60 with high‑risk AML or high‑risk MDS who are eligible for myeloablative allogeneic stem cell transplantation and meet the trial’s genetic and disease‑risk criteria.
Not a fit: Patients older than 60, those unfit for myeloablative conditioning, those with uncontrolled infection or severe organ dysfunction, or those with contraindications to venetoclax may not receive benefit from this approach.
Why it matters
Potential benefit: If successful, adding venetoclax to conditioning could reduce post‑transplant relapse and improve relapse‑free and overall survival for high‑risk AML and MDS patients.
How similar studies have performed: Venetoclax has shown meaningful benefits when combined with chemotherapy or hypomethylating agents in AML, but adding venetoclax directly to myeloablative conditioning regimens is relatively novel and has limited randomized data.
Eligibility criteria
Show full inclusion / exclusion 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)
Where this trial is running
Hangzhou, Zhejiang
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.