G-CSF+DAC+BUCY vs G-CSF+DAC+BF Conditioning Regimen for High-risk MDS Undergoing Allo-HSCT

Study Overview
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Brief Summary
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Allo-HSCT is the most effective way to cure high-risk MDS patients. At present, the best conditioning regimen for high-risk MDS patients undergoing allo-HSCT remains in discussion. In this prospective study, the safety and efficacy of G-CSF+DAC+BUCY and G-CSF+DAC+BF conditioning regimens in high-risk MDS patients undergoing allo-HSCT are evaluated.

Detailed Description
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Allo-HSCT is the most effective way to cure high-risk MDS patients. At present, the best conditioning regimen for high-risk MDS patients undergoing allo-HSCT remains in discussion. A previous study by the investigators has showed that G-CSF +DAC+BUCY conditioning regimen could reduce the relapse and improve the survival compared with BUCY conditioning regimen, while the two conditioning regimens both have high non-relapse mortality (NRM). Several retrospective and prospective studies have demonstrated that BF conditioning regimen has a lower NRM compared with BUCY conditioning regimen, while the relapse and survival are similar in patients undergoing BF and BUCY conditioning regimens. Based on the above, the investigators design the prospective randomized controlled study to evaluate the safety and efficacy of G-CSF+DAC+BUCY and G-CSF+DAC+BF conditioning regimens in high-risk MDS patients undergoing allo-HSCT.

Official Title
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G-CSF+DAC+BUCY vs. G-CSF+DAC+BF Conditioning Regimen for Patients With High-risk MDS Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Myelodysplastic Syndrome, Allogeneic Hematopoietic Stem Cell Transplantation, Conditioning

Intervention / Treatment
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* Drug: Granulocyte Colony-Stimulating Factor(G-CSF)
* Drug: Decitabine (DAC)
* Drug: Busulfan
* Drug: Fludarabine (FLU)
* Drug: Cyclophosphamide (CY)
* Drug: Busulfan (BU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had a diagnosis of RAEB-1 or RAEB-2 with IPSS-R >3 Age 18 to 65 years old ECOG performance status of 0-2 HCT-CI of 0-2 Were willing to undergo allo-HSCT Exclusion Criteria: Therapy-related MDS Previous allo-HSCT Uncontrolled infections Liver or renal dysfunction Severe concomitant conditions not suitable for the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF+DAC+BF<br>For patients with high-risk MDS undergoing allo- HSCT, Granulocyte Colony-Stimulating Factor (G-CSF)+Decitabine+BF conditioning regimen was G-CSF 5ug/kg/day on days -17 to -10 (when white blood cell is more than 20G/L, stop using G-CSF), Decitabine 20mg/m2/day on days -14 to -10, Busulfan (BU) 3.2 mg/kg/day on days -6 to -3, Fludarabine (FLU) 30mg/m2/ day on days -7 to -3. | Drug: Granulocyte Colony-Stimulating Factor(G-CSF)<br>* G-CSF was administered at 5 ug/kg/day on days-17 to -10. When white blood cell is more than 20G/L, stop using G-CSF.<br>Drug: Decitabine (DAC)<br>* Decitabine was administered at 20mg/m2/day on days -14 to -10.<br>Drug: Fludarabine (FLU)<br>* Fludarabine was administered at 30 mg/m2/day on days -7 to -3.<br>Drug: Busulfan (BU)<br>* Busulfan was administered at 3.2 mg/kg/day on days -6 to -3 in G-CSF+DAC +BF group.<br>|
| Active Comparator: G-CSF+DAC+BUCY<br>For patients with high-risk MDS undergoing allo- HSCT, Granulocyte Colony -Stimulating Factor (G-CSF)+Decitabine+BUCY conditioning regimen was G-CSF 5ug/kg/day on days -17 to -10 (when white blood cell is more than 20G/L, stop using G-CSF), Decitabine 20mg/m2/day on days -14 to -10, Busulfan (BU) 3.2 mg/kg/day on days -7 to -4, Cyclophosphamide (CY) 60 mg/kg/day on days -3, -2. | Drug: Granulocyte Colony-Stimulating Factor(G-CSF)<br>* G-CSF was administered at 5 ug/kg/day on days-17 to -10. When white blood cell is more than 20G/L, stop using G-CSF.<br>Drug: Decitabine (DAC)<br>* Decitabine was administered at 20mg/m2/day on days -14 to -10.<br>Drug: Busulfan<br>* Busulfan was administered at 3.2 mg/kg/day on days -7 to -4 in G-CSF+DAC+BUCY group.<br>Drug: Cyclophosphamide (CY)<br>* Cyclophosphamide was administered at 60 mg/kg/day on days -3,-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse mortality (NRM) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | 1 year | 
| Disease-free survival (DFS) |  | 1 year | 
| Cumulative incidence of relapse |  | 1 year | 
| Adverse effects |  | within 100 days post-transplantation |