VEN+DAC+Bu2Flu4 vs Bu2Flu5 Conditioning Regimen for Elderly Myeloid Malignancies Undergoing Allo-HSCT

Not Applicable

Not yet recruiting

• Conditions: Older Patients; Myeloid Malignancies; Conditioning; Hematopoietic Stem Cell Transplantation (HSCT)
• Interventions: Drug: Venetoclax (VEN); Drug: Decitabine (DAC); Drug: Busulfan (Bu); Drug: Fludarabine (Flu)

• Registration Number: NCT07052422
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

The purpose of this study is to compare the efficacy and safety of venetoclax+decitabine+busulfan+fludarabine (VEN+DAC+Bu2Flu4) regimen with busulfan+fludarabine (Bu2Flu5) regimen in older patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potent curative approach for myeloid malignancies, but outcomes post-transplantation of older population were unsatisfactory. The conditioning regimen is an essential factor affecting outcomes post-transplantation. Currently, the optimal conditioning for older patients with myeloid malignancies remains unclear. Myeloablative conditioning (MAC) regimens like busulfan plus cyclophosphamide, and busulfan plus fludarabine (Bu4Flu4-5) have low relapse rates, but high non-relapse mortality (NRM) is observed in older patients with myeloid malignancies. The development of reduced-intensity conditioning (RIC) regimens such as Bu2Flu5 has decreased NRM and enhanced the feasibility of allo-HSCT in older patients with myeloid malignancies, but it appears to have higher relapse rate. Neither conventional MAC nor RIC regimens benefit older patients with myeloid malignancies. In recent years, some studies reported that the introduction of venetoclax (VEN) or decitabine (DAC) to MAC reduced relapse without increasing NRM in younger patients with high-risk myeloid malignancies. However, whether VEN and DAC combined with RIC regimen reduce relapse without increasing NRM, then improve survival in older patients with myeloid malignancies is unclear. Therefore, we conducted a randomized controlled study to compare the efficacy and safety of VEN+DAC+Bu2Flu4 with Bu2Flu5 in older patients with myeloid malignancies undergoing allo-HSCT.

Study Timeline

• Study First Submitted: 2025-06-22
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-01
• Last Update Submitted: 2025-07-01
• Study First Posted: 2025-07-04
• Last Update Posted: 2025-07-04
• Study Start: 2025-07-15
• Primary Completion: 2027-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

• 60-75 years
• Acute myeloid leukaemia in first complete remission or myelodysplastic syndrome
• Willing to undergo the first allo-HSCT
• Eastern Cooperative Oncology Group performance status of 0-2

Exclusion Criteria

• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (investigators' decision)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VEN+DAC+Bu2Flu4	Venetoclax (VEN)	Venetoclax+Decitabine+Busulfan+Fludarabine
VEN+DAC+Bu2Flu4	Decitabine (DAC)	Venetoclax+Decitabine+Busulfan+Fludarabine
VEN+DAC+Bu2Flu4	Busulfan (Bu)	Venetoclax+Decitabine+Busulfan+Fludarabine
VEN+DAC+Bu2Flu4	Fludarabine (Flu)	Venetoclax+Decitabine+Busulfan+Fludarabine
Bu2Flu5	Busulfan (Bu)	Busulfan+Fludarabine
Bu2Flu5	Fludarabine (Flu)	Busulfan+Fludarabine

Primary Outcome Measures

Name	Time	Method
Disease-free survival (DFS) rate	2 year	Will calculate time from random assignment until disease progression or relapse or death from any cause

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS) rate	2 year	Will calculate time from random assignment until death from any cause.
Relapse incidence	2 year	Will calculate time from random assignment until relapse or disease progression.
Non-relapse mortality (NRM) incidence	2 year	Defined as death from any cause not subsequent to relapse or disease progression.