Outcomes of Patients After Allo-HSCT With Decitabine and NAC

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04945096

Collaborator

(none)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Engraft Failure Relapse GVHD	Drug: decitabine Drug: Acetylcysteine Drug: Semustine Drug: Cytarabine Drug: Busulfan Drug: Cyclophosphamide Drug: Cyclosporin A Drug: Anti-thymocyte globulin Drug: Mycophenolate	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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).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)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Acetylcysteine + decitabine

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

Decitabine (20mg/m2 intravenously from day -10 to day -8 of conditional regimen)

Other Names:

5-aza-2'-deoxycytidine

Drug: Acetylcysteine

Acetylcysteine: 1.2g twice a day, oral administration, from day -10 to day 365 after HSCT.

Other Names:

Acetadote

Drug: Semustine

Semustine: 250 mg/m2/day on day -9.

Other Names:

Methyl-CCNU

Drug: Cytarabine

Cytarabine: 2 g/m2 every 12 hours on day -8.

Other Names:

Cytosine arabinoside

Drug: Busulfan

Busulfan: 3.2mg/kg/day on day -7 to -5.

Other Names:

Myleran

Drug: Cyclophosphamide

Cyclophosphamide: 1.8g/m2/day on day -4 to -3.

Other Names:

Cytoxan

Drug: Cyclosporin A

Cyclosporin A: 3mg/kg/d from day -8.

Other Names:

Cyclosporine

Drug: Anti-thymocyte globulin

Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) will be added for transplants with unrelated donor or HLA mismatched donor.

Other Names:

Thymoglobulin

Drug: Mycophenolate

Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor.

Other Names:

CellCept

Active Comparator: Standard Treatment

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

Semustine: 250 mg/m2/day on day -9.

Other Names:

Methyl-CCNU

Drug: Cytarabine

Cytarabine: 2 g/m2 every 12 hours on day -8.

Other Names:

Cytosine arabinoside

Drug: Busulfan

Busulfan: 3.2mg/kg/day on day -7 to -5.

Other Names:

Myleran

Drug: Cyclophosphamide

Cyclophosphamide: 1.8g/m2/day on day -4 to -3.

Other Names:

Cytoxan

Drug: Cyclosporin A

Cyclosporin A: 3mg/kg/d from day -8.

Other Names:

Cyclosporine

Drug: Anti-thymocyte globulin

Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) will be added for transplants with unrelated donor or HLA mismatched donor.

Other Names:

Thymoglobulin

Drug: Mycophenolate

Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor.

Other Names:

CellCept

Outcome Measures

Primary Outcome Measures

The hematological engraftment rates [1 year]
The hematological engraftment rates of patients after HSCT.
GVHD rates [1 year]
The GVHD rates of patients after HSCT.
Relapse rates [1 year]
The relapse rates of patients after HSCT.

Secondary Outcome Measures

Overall survival [1 year]
To evaluate the overall survival (days) of patients after HSCT.
Disease free survival [1 year]
To evaluate the disease free survival (days) of patients after HSCT.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.