Venetoclax+Decitabine+Busulfan+Fludarabine (VEN+DAC+Bu2Flu4) vs Busulfan+Fludarabine Conditioning Regimen (Bu2Flu5 ) for Older Patients With Myeloid Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 160
- Primary Endpoint
- Disease-free survival (DFS) rate
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
VEN+DAC+Bu2Flu4
Venetoclax+Decitabine+Busulfan+Fludarabine
Intervention: Venetoclax (VEN) (Drug)
VEN+DAC+Bu2Flu4
Venetoclax+Decitabine+Busulfan+Fludarabine
Intervention: Decitabine (DAC) (Drug)
VEN+DAC+Bu2Flu4
Venetoclax+Decitabine+Busulfan+Fludarabine
Intervention: Busulfan (Bu) (Drug)
VEN+DAC+Bu2Flu4
Venetoclax+Decitabine+Busulfan+Fludarabine
Intervention: Fludarabine (Flu) (Drug)
Bu2Flu5
Busulfan+Fludarabine
Intervention: Busulfan (Bu) (Drug)
Bu2Flu5
Busulfan+Fludarabine
Intervention: Fludarabine (Flu) (Drug)
Outcomes
Primary Outcomes
Disease-free survival (DFS) rate
Time Frame: 2 year
Will calculate time from random assignment until disease progression or relapse or death from any cause
Secondary Outcomes
- Overall survival (OS) rate(2 year)
- Relapse incidence(2 year)
- Non-relapse mortality (NRM) incidence(2 year)
