Outcomes of Patients After Allo-HSCT With Decitabine and NAC

Study Overview
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Brief Summary
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The investigators will conduct this prospective and randomized clinical trial, to evaluate the hematopoietic reconstitution, GVHD and relapse rate of patients after allo-HSCT with decitabine containing conditional regimen and NAC treatment.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative treatment for hematological malignancy. Relapse, graft versus host disease (GVHD) and graft failure are the main causes of treatment failure. Acetylcysteine (NAC) was found to be able to enhance defective HSCs by repairing dysfunctional bone marrow endothelial cells, and overcome the exhaustion of HSCs and enhance the engraftment of HSCs. Decitabine could restore bone marrow microenvironment by repairing endothelial cells and endothelial progenitor cells, as well as cytokines and chemokines which are crucial to HSCs proliferation and differentiation, thereby promote platelet recovery after HSCT. Besides, decitabine therapy was shown to be associated with reduced incidence of GVHD, lower relapse rate, and increased overall survival in several studies. Thereby the investigators will conduct this clinical trial to evaluate the hematopoietic reconstitution, GVHD and relapse rate of patients with hematological malignancy after allo-HSCT with decitabine containing conditional regimen and NAC treatment.

Official Title
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Outcomes of Patients After Allogenic Hematopoietic Cell Transplantation With Decitabine-containing Conditioning Regimen and Acetylcysteine Treatment

Conditions
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Engraft Failure, Relapse, GVHD

Intervention / Treatment
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* Drug: decitabine
* Drug: Acetylcysteine
* Drug: Semustine
* Drug: Cytarabine
* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Cyclosporin A
* Drug: Anti-thymocyte globulin
* Drug: Mycophenolate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as hematopoietic malignancy; Achieved complete remission since the last chemotherapy; Age 10-70 years； Be willing to receive allo-HSCT, with HLA matched related or HLA matched unrelated, or HLA mismatched related donor. Exclusion Criteria: Active infections, severe organ damage (cardiac, renal and/or hepatic dysfunction greater than grade 2 according to the Common Terminology Criteria for Adverse Events V5.0), or any other conditions that make patients ineligible for allo-HSCT; Allergic to acetylcysteine or decitabine.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 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
Interventional Model Description: Subjects will be randomized after the investigator has verified that all eligibility criteria have been met. Subjects will be randomized in a 1:1 ratio to either Experimental Group (Acetylcysteine + Decitabine) or Active Comparator Group (Standard Treatment).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylcysteine + decitabine<br>Acetylcysteine (1.2g twice a day, oral administration, from day -10 to day 365 after HSCT). Conditional regimen: decitabine (20mg/m2 intravenously from day -10 to day -8 of conditional regimen); semustine 250 mg/m2/day on day -9; cytarabine 2 g/m2 every 12 hours on day -8; busulfan 3.2mg/kg/day on day -7 to -5; cyclophosphamide 1.8g/m2/day on day -4 to -3; cyclosporin A: 3mg/kg/d from day -8. Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) and mycophenolate (500mg, oral, twice a day from day -8) were usually added for transplants with unrelated donor or HLA mismatched donor. | Drug: decitabine<br>* Decitabine (20mg/m2 intravenously from day -10 to day -8 of conditional regimen)<br>* Other names: 5-aza-2'-deoxycytidine;Drug: Acetylcysteine<br>* Acetylcysteine: 1.2g twice a day, oral administration, from day -10 to day 365 after HSCT.<br>* Other names: Acetadote;Drug: Semustine<br>* Semustine: 250 mg/m2/day on day -9.<br>* Other names: Methyl-CCNU;Drug: Cytarabine<br>* Cytarabine: 2 g/m2 every 12 hours on day -8.<br>* Other names: Cytosine arabinoside;Drug: Busulfan<br>* Busulfan: 3.2mg/kg/day on day -7 to -5.<br>* Other names: Myleran;Drug: Cyclophosphamide<br>* Cyclophosphamide: 1.8g/m2/day on day -4 to -3.<br>* Other names: Cytoxan;Drug: Cyclosporin A<br>* Cyclosporin A: 3mg/kg/d from day -8.<br>* Other names: Cyclosporine;Drug: Anti-thymocyte globulin<br>* Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) will be added for transplants with unrelated donor or HLA mismatched donor.<br>* Other names: Thymoglobulin;Drug: Mycophenolate<br>* Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor.<br>* Other names: CellCept;|
| Active Comparator: Standard Treatment<br>Conditional regimen: semustine 250 mg/m2/day on day -9; cytarabine 2 g/m2 every 12 hours on day -8; busulfan 3.2mg/kg/day on day -7 to -5; cyclophosphamide 1.8g/m2/day on day -4 to -3; cyclosporin A: 3mg/kg/d from day -8. Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) and mycophenolate (500mg, oral, twice a day from day -8) were usually added for transplants with unrelated donor or HLA mismatched donor. | Drug: Semustine<br>* Semustine: 250 mg/m2/day on day -9.<br>* Other names: Methyl-CCNU;Drug: Cytarabine<br>* Cytarabine: 2 g/m2 every 12 hours on day -8.<br>* Other names: Cytosine arabinoside;Drug: Busulfan<br>* Busulfan: 3.2mg/kg/day on day -7 to -5.<br>* Other names: Myleran;Drug: Cyclophosphamide<br>* Cyclophosphamide: 1.8g/m2/day on day -4 to -3.<br>* Other names: Cytoxan;Drug: Cyclosporin A<br>* Cyclosporin A: 3mg/kg/d from day -8.<br>* Other names: Cyclosporine;Drug: Anti-thymocyte globulin<br>* Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) will be added for transplants with unrelated donor or HLA mismatched donor.<br>* Other names: Thymoglobulin;Drug: Mycophenolate<br>* Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor.<br>* Other names: CellCept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The hematological engraftment rates | The hematological engraftment rates of patients after HSCT. | 1 year | 
| GVHD rates | The GVHD rates of patients after HSCT. | 1 year | 
| Relapse rates | The relapse rates of patients after HSCT. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To evaluate the overall survival (days) of patients after HSCT. | 1 year | 
| Disease free survival | To evaluate the disease free survival (days) of patients after HSCT. | 1 year |