Adding venetoclax to fludarabine–melphalan conditioning for people over 50 with AML or MDS getting a donor stem cell transplant

Fludarabine Plus Melphalan Versus Addition of Venetoclax to Fludarabine/Melphalan Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in AML/MDS Patients Aged > 50 Years: a Multicenter, Randomized, Phase 3 Trial

This tests whether adding venetoclax to standard fludarabine–melphalan conditioning helps people over 50 with AML or MDS who are having an allogeneic stem cell transplant.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 186 (estimated)
• Ages: 50 Years to 75 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (other)
• Drugs / interventions: chemotherapy, Fludarabine
• Locations: 18 sites (Fuzhou, Fujian and 17 other locations)
• Trial ID: NCT07396480 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized Phase 3 trial enrolling patients older than 50 with acute myeloid leukemia in remission or higher‑risk myelodysplastic syndromes who are planned for allogeneic hematopoietic stem cell transplantation. Participants are stratified by age and disease (AML vs MDS) and randomized to receive either standard fludarabine plus melphalan conditioning or the same regimen with venetoclax added. Venetoclax is given orally days −8 to −2 with antifungal drug–based dose adjustments, and melphalan dose is adjusted by patient age. The trial compares transplant outcomes including relapse, survival, and safety between the two arms across several Chinese transplant centers.

Who should consider this trial

Good fit: Adults older than 50 with AML in remission or intermediate‑to‑high/very high–risk MDS (or MDS/MPN) who have an eligible related or unrelated donor and meet organ function and performance criteria (Karnofsky ≥70, ECOG <3) are appropriate candidates.

Not a fit: Patients with significant cardiac dysfunction (e.g., LVEF <60%), severe arrhythmia, uncontrolled comorbidities, or those who are not eligible for allogeneic transplantation are unlikely to benefit from this conditioning strategy.

Why it matters

Potential benefit: If successful, adding venetoclax could reduce relapse and improve post‑transplant survival for older adults with AML or high‑risk MDS.

How similar studies have performed: Venetoclax has shown clear activity in combination therapies for AML in non‑transplant settings, but its addition specifically to transplant conditioning is relatively novel with limited prior data supporting efficacy in this exact context.

Eligibility criteria

Inclusion Criteria:

1. Aged \> 50 years;
2. Confirmed as acute myeloid leukemia (AML) in remission prior to transplantation, myelodysplastic syndrome (MDS; IPSS: Intermediate-2, high; or IPSS-R: Intermediate, high, very high; or IPSS-M: moderate-high, high, and very high), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) by morphology, immunology, cytogenetics and molecular biology (MICM) typing;
3. Having an eligible donor and scheduled to undergo allogeneic hematopoietic stem cell transplantation (Allo-HCT) from a related or unrelated donor;
4. Karnofsky Performance Score ≥ 70;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status \< 3;
6. Expected survival time \> 12 weeks;
7. Voluntarily signing the informed consent form and being able to understand and comply with all study requirements.

Exclusion Criteria:

1. Complicated with severe cardiac insufficiency with a left ventricular ejection fraction (EF) \< 60%; or complicated with severe arrhythmia, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
2. Complicated with severe pulmonary insufficiency (obstructive and/or restrictive ventilatory disorder), and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
3. Complicated with severe liver function impairment, with liver function indicators (alanine aminotransferase \[ALT\], total bilirubin \[TBIL\]) exceeding 3 times the upper limit of normal (ULN); and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
4. Complicated with severe renal insufficiency, with serum creatinine (Cr) exceeding 2 times the upper limit of normal (ULN); or with a 24-hour creatinine clearance rate (Ccr) \< 50 ml/min, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
5. Suffering from severe active infection prior to transplantation, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
6. Having a history of allergic reactions or severe adverse reactions to the drugs involved in the conditioning regimen, and assessed by the investigator as ineligible for enrollment;
7. Other reasons for ineligibility assessed by the investigator.

Where this trial is running

Fuzhou, Fujian and 17 other locations

• The First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (RECRUITING)
• Nanfang Hospital Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (RECRUITING)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)
• Xiangya Hospital Central South University — Changsha, Hunan, China (RECRUITING)
• Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) — Nanjing, Jiangsu, China (RECRUITING)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (RECRUITING)
• the First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)
• Zhejiang Cancer Hospital & Hangzhou Institute of Medicine, Chinese Academy of Sciences — Hangzhou, Zhejiang, China (RECRUITING)
• Second Affiliated Hospital of Army Medical University (Xinqiao Hospital) — Chongqing, China (RECRUITING)
• Sir Run Run Shaw Hospital Zhejiang University School of Medicine — Hangzhou, China (RECRUITING)
• The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine) — Hangzhou, China (RECRUITING)
• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, China (RECRUITING)
• Zhejiang Provincial Peoples's Hospital — Hangzhou, China (RECRUITING)
• The Affiliated People's Hospital of Ningbo University — Ningbo, China (RECRUITING)
• The First Affiliated Hospital of Ningbo University — Ningbo, China (RECRUITING)
• Shanghai General Hospital (Shanghai First People's Hospital) — Shanghai, China (RECRUITING)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, China (RECRUITING)

Study contacts

• Study coordinator: Yi Luo, Professor

Conditions: Venentoclax, Myeloid Malignancies, Conditioning, ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, Acute Myeloid Leucemia, Myeldysplastic Syndrome