Engraft Failure, Relapse, GVHD
Conditions
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.
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.
Interventions
DRUGdecitabine
Decitabine (20mg/m2 intravenously from day -10 to day -8 of conditional regimen)
DRUGAcetylcysteine
Acetylcysteine: 1.2g twice a day, oral administration, from day -10 to day 365 after HSCT.
DRUGSemustine
Semustine: 250 mg/m2/day on day -9.
DRUGCytarabine
Cytarabine: 2 g/m2 every 12 hours on day -8.
DRUGBusulfan
Busulfan: 3.2mg/kg/day on day -7 to -5.
DRUGCyclophosphamide
Cyclophosphamide: 1.8g/m2/day on day -4 to -3.
DRUGCyclosporin A
Cyclosporin A: 3mg/kg/d from day -8.
DRUGAnti-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.
DRUGMycophenolate
Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor.
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
10 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed as hematopoietic malignancy; 2. Achieved complete remission since the last chemotherapy; 3. Age 10-70 years； 4. Be willing to receive allo-HSCT, with HLA matched related or HLA matched unrelated, or HLA mismatched related donor.
Exclusion criteria
1. 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; 2. Allergic to acetylcysteine or decitabine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Contacts
Primary ContactYaqiong Tang, Dr.
Backup ContactYue Han, Prof.
Outcome results
None listed