Outcomes of Patients After Allo-HSCT With Decitabine and NAC

Soochow University

Status and phase: Not yet enrolling; Phase 3

Conditions: Engraft Failure; Relapse; GVHD

Treatments: Drug: Cyclophosphamide; Drug: Anti-thymocyte globulin; Drug: decitabine; Drug: Acetylcysteine; Drug: Semustine; Drug: Mycophenolate; Drug: Busulfan; Drug: Cytarabine; Drug: Cyclosporin A

Study type: Interventional

Funder types: Other

Identifiers

NCT04945096

SOOCHOW-HY-2021-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 10 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Acetylcysteine + decitabine

Experimental group

Description:

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.

Treatment:

Drug: Cyclosporin A

Drug: Cytarabine

Drug: Mycophenolate

Drug: Busulfan

Drug: Semustine

Drug: Acetylcysteine

Drug: decitabine

Drug: Anti-thymocyte globulin

Drug: Cyclophosphamide

Standard Treatment

Active Comparator group

Description:

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.

Treatment:

Drug: Cyclosporin A

Drug: Cytarabine

Drug: Mycophenolate

Drug: Busulfan

Drug: Semustine

Drug: Anti-thymocyte globulin

Drug: Cyclophosphamide