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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetylcysteine + decitabine | Experimental | 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. |
|
| Standard Treatment | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| decitabine | Drug | Decitabine (20mg/m2 intravenously from day -10 to day -8 of conditional regimen) |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yaqiong Tang, Dr. | Contact | 18896588075 | tangyaqiong@suda.edu.cn | |
| Yue Han, Prof. | Contact | 13901551669 | hanyue@suda.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Yue Han, Prof. | The First Affiliated Hospital of Soochow University | Study Chair |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Apr 25, 2021 | Jun 17, 2021 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D000111 | Acetylcysteine |
| D012673 | Semustine |
| D003561 | Cytarabine |
| D002066 | Busulfan |
| D003520 | Cyclophosphamide |
| D016572 | Cyclosporine |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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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).
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| Acetylcysteine | Drug | Acetylcysteine: 1.2g twice a day, oral administration, from day -10 to day 365 after HSCT. |
|
|
| Semustine | Drug | Semustine: 250 mg/m2/day on day -9. |
|
|
| Cytarabine | Drug | Cytarabine: 2 g/m2 every 12 hours on day -8. |
|
|
| Busulfan | Drug | Busulfan: 3.2mg/kg/day on day -7 to -5. |
|
|
| Cyclophosphamide | Drug | Cyclophosphamide: 1.8g/m2/day on day -4 to -3. |
|
|
| Cyclosporin A | Drug | Cyclosporin A: 3mg/kg/d from day -8. |
|
|
| Anti-thymocyte globulin | Drug | Anti-thymocyte globulin (2mg/kg/d on day -5 to day -2) will be added for transplants with unrelated donor or HLA mismatched donor. |
|
|
| Mycophenolate | Drug | Mycophenolate (500mg, oral, twice a day from day -8) will be added for transplants with unrelated donor or HLA mismatched donor. |
|
|
| 1 year |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008130 | Lomustine |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
| D001087 | Arabinonucleosides |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |