Acute Myeloid Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation, Conditioning
Conditions
Brief summary
The purpose of this prospective, open-label, randomized multicenter study is to evaluate the safety and efficacy of low dose decitabine in combination with modified BUCY vs modified BUCY as a myeloablative conditioning regimen for high-risk patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
Detailed description
Allo-HSCT is the most effective treatment stratagey for high risk acute myeloid leukemia. At present, modified BUCY is the standard conditioning regimen for AML undergoing allo-HSCT in our institute. However, relapse occured in as high as 30-50% high risk AML patients after allo-HSCT. Thus, the best conditioning regimen for this subgroup remains to be optimized. Low dose decitabine in combination with chemotherapy have been shown to improve comple remission rate of high risk AML patients. To reduce the relapse rate after allo-HSCT, low dose decitabine is added in the modified BUCY regimen. In this study, the safety and efficacy of low dose decitabine + modified BUCY vs modified BUCY myeloablative conditioning regimens in high risk undergoing allo-HSCT are evaluated.
Interventions
DRUGDecitabine plus Modified BUCY
Decitabine:20 mg/m²/day on day -14 to -10; Modified BUCY: 1. Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 2. Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 3. Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.
DRUGModified BUCY
1. Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 2. Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 3. Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Jiangsu University
Xuzhou Medical University
Southeast University, China
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Age 12 to 60 years. * Diagnosis of high-risk acute myeloid leukemia at the time of transplant. (High-risk AML features are defined by the following: relapsed or primary refractory AML; Secondary AML（AML Secondary to myelodysplastic syndrome(MDS) or treatment-related AML); extramedullary leukemia; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, or deletion of 5q; or presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio.) * Patient must have adequate pre-transplant organ function.
Exclusion criteria
* Age \<12 or \>60 years. * Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen. * Any other severe concurrent diseases, or have a history of serious organ dysfunction. * Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| disease-free survival (DFS) | 3 year | time from randomization to the first of reccurrence or death |
| overall survival (OS) | 3 year | time from randomization to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| veno-occlusive disease (VOD) | 3 year | incidence of veno-occlusive disease (VOD) events |
| graft-versus-host disease (GvHD) | 3 year | incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) |
| transplant related mortality （TRM） | 3 year | cumulative incidence of transplant related mortality |
| relapse | 3 year | cumulative incidence of relapse |
Countries
China
Contacts
Primary ContactXiaowen Tang, MD
Backup ContactDepei Wu, MD
Outcome results
None listed