Low Dose Decitabine + Modified BUCY Conditioning Regimen for High Risk Acute Myeloid Leukemia Undergoing Allo-HSCT

Study Overview
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Brief Summary
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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
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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.

Official Title
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Low Dose Decitabine + Modified BUCY Conditioning Regimen for High Risk Acute Myeloid Leukemia Undergoing Allo-HSCT

Conditions
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Allogeneic Hematopoietic Stem Cell Transplantation, Conditioning, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Decitabine plus Modified BUCY
* Drug: Modified BUCY


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine plus Modified BUCY<br>For high-risk patients with Acute Myeloid Leukemia (AML) undergoing allo-HSCT, The Decitabine plus Modified BuCy regimen consisted of decitabine,semustine,cytarabine, busulfan and cyclophosphamide. | Drug: Decitabine plus Modified BUCY<br>* Decitabine:20 mg/m²/day on day -14 to -10; Modified BUCY: 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. 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. 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.<br>|
| Active Comparator: Modified BUCY<br>For high-risk patients with Acute Myeloid Leukemia (AML) undergoing allo-HSCT, The Modified BuCy regimen consisted of semustine,cytarabine, busulfan and cyclophosphamide. | Drug: Modified BUCY<br>* 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. 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. 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival (DFS) | time from randomization to the first of reccurrence or death | 3 year | 
| overall survival (OS) | time from randomization to death from any cause | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| veno-occlusive disease (VOD) | incidence of veno-occlusive disease (VOD) events | 3 year | 
| graft-versus-host disease (GvHD) | incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) | 3 year | 
| transplant related mortality （TRM） | cumulative incidence of transplant related mortality | 3 year | 
| relapse | cumulative incidence of relapse | 3 year |