Older Patients, Myeloid Malignancies, Conditioning, Hematopoietic Stem Cell Transplantation (HSCT)
Conditions
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.
Interventions
DRUGVenetoclax (VEN)
Venetoclax (VEN) was administered at 400mg/day on days -10 to -4.
DRUGDecitabine (DAC)
Decitabine (DAC) was administered at 20mg/m2/day on days -10 to -8.
DRUGBusulfan (Bu)
Busulfan (Bu) was administered at 3.2 mg/kg/day on days -5 to -4.
Fludarabine (Flu) was administered at 30mg/m2/day on days -5 to -2.
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival (DFS) rate | 2 year | Will calculate time from random assignment until disease progression or relapse or death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Contacts
Primary ContactQifa Liu
Backup ContactQifa Liu
Outcome results
None listed