NCT07396480 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
| NCT ID | NCT07396480 |
| Status | Recruiting |
| Phase | Phase 3 |
| Sponsor | First Affiliated Hospital of Zhejiang University |
| Condition | Venentoclax |
| Study Type | INTERVENTIONAL |
| Enrollment | 186 participants |
| Start Date | 2026-03-01 |
| Primary Completion | 2030-01-31 |
Eligibility & Interventions
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.
This trial targets 186 participants in total. It began in 2026-03-01 with a primary completion date of 2030-01-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) serves as a curative treatment modality for the vast majority of patients with hematological malignancies. Historically, due to the relatively high treatment-related mortality rate associated with Allo-HCT, this therapy was primarily administered to younger patients. However, the median age at onset of most hematological malignancies falls within the elderly population. For instance, the median ages at onset of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are 68 and 77 years, respectively. In recent years, with the advancement of transplantation techniques and the application of Reduced-intensity Conditioning (RIC) regimens, a growing number of elderly patients have undergone Allo-HCT. Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) indicate that in 2017, 31% of patients who received Allo-HCT were aged over 60 years, and 6% were over 70 years old. Over the past decade, the number of elderly patients undergoing Allo-HCT has increased significantly. Given that most elderly patients cannot tolerate conventional myeloablative conditioning regimens, RIC regimens based on Fludarabine (Flu) combined with Busulfan (Bu), or Fludarabine (Flu) combined with Melphalan (Mel) are currently widely used in elderly patients undergoing Allo-HCT. Nevertheless, the post-transplant relapse rate remains as high as 30%-55%, and the long-term GVHD-free and Relapse-free Survival (GRFS) rate fluctuates between 21% and 59%, suggesting that the efficacy of transplantation needs to be further improved. Further comparison of the commonly used RIC regimens in elderly patients-namely Flu+Bu (2-day), Flu+Bu (4-day) and Flu+Mel-has demonstrated that the Flu+Mel regimen yields superior transplantation outcomes over the Flu+Bu regimens. At present, the optimal RIC regimen for elderly patients with hematological malignancies has not yet been clearly defined. The selection of transplantation conditioning regimens for elderly patients should strike a balance between reducing non-relapse mortality and decreasing post-transplant relapse. Over the past 20 years, an increasing number of targeted drugs acting on specific cellular signaling pathways, anti-apoptotic proteins, epigenetic regulators, and monoclonal antibodies have been introduced into clinical practice, thereby revolutionizing the treatment landscape of hematological malignancies. These novel targeted therapies not only bring hope of achieving remission to patients with hematological tumors resistant to traditional chemotherapy, but also the combined application of novel drugs and Allo-HCT is bound to fundamentally transform the overall technical system of hematopoietic stem cell transplantation. Venetoclax is a potent and selective oral inhibitor targeting the BH3 domain of the anti-apoptotic protein Bcl-2. In 2018, the FDA approved Venetoclax as a first-line induction chemotherapy agent for elderly AML patient's ineligible for intensive chemotherapy, with a complete remission rate of up to 67% and favorable tolerability¹¹. Preclinical studies using Allo-HCT animal models have confirmed that the addition of a Bcl-2 inhibitor to RIC regimens can promote donor cell engraftment, reduce the incidence of GVHD, without impairing the graft-versus-leukemia (GVL) effect¹². In recent years, clinical trials have reported the efficacy and safety of the conditioning regimen combining Venetoclax with Flu+Bu in patients with myeloid malignancies undergoing Allo-HCT. Our research center has demonstrated the favorable safety profile and promising long-term survival outcomes of the Venetoclax plus Flu+Mel conditioning regimen in a phase II clinical trial involving patients aged over 50 years with AML/MDS undergoing Allo-HCT (2024 EBMT Poster B093; 2025 EBMT Poster B126). However, the long-term superiority of this novel regimen over the conventional Flu+Mel conditioning regimen remains to be clarified. Therefore, based on the existing findings from clinical studies and Allo-HCT animal model research, we hypothesize that incorporating Venetoclax into the Fludarabine+Melphalan conditioning regimen for elderly patients undergoing Allo-HCT is expected to improve long-term post-transplant survival and further enhance the transplantation efficacy in this patient population.
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.
Contact & Investigator
Frequently Asked Questions
Who can join the NCT07396480 clinical trial?
This trial is open to participants of all sexes, aged 50 Years or older, up to 75 Years, studying Venentoclax. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT07396480 trial and what does that mean for participants?
Phase 3 trials are large-scale studies comparing the new treatment to existing standards of care or a placebo. They provide the evidence needed for regulatory approval. This trial targets 186 participants.
Is NCT07396480 currently recruiting?
Yes, NCT07396480 is actively recruiting participants. Contact the research team at luoyijr@zju.edu.cn for enrollment information.
Where is the NCT07396480 trial being conducted?
This trial is being conducted at Fuzhou, China, Guangzhou, China, Zhengzhou, China, Wuhan, China and 11 additional locations.
Who is sponsoring the NCT07396480 clinical trial?
NCT07396480 is sponsored by First Affiliated Hospital of Zhejiang University. The trial plans to enroll 186 participants.