The Use of N-acetylcysteine for Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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We aim to assess the the efficiency and safety of N-acetylcysteine for prevention of thrombotic events after allogenic hematopoietic stem cell transplantation.

Detailed Description
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The thrombotic events are increasingly recognized complications of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality, which include transplantation-associated thrombotic microangiopathy (TA-TMA), sinusoidal obstructive syndrome (SOS), deep vein thrombosis (DVT), pulmonary thromboembolism (PTE), catheter-related thrombosis (CRT), superficial vein thrombosis (SVT), etc. There is a complex interplay on balancing the risk for thrombosis and bleeding in these patients, making treatment decisions particularly challenging. Emerging studies revealed that endothelial injury is the common underlying mechanism among different thrombotic disorders. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction by inhibiting ROS production and preventing endothelial apoptosis. Our previous study showed low dose NAC could decrease the incidence of TA-TMA. In this study, we aim to assess the the efficiency and safety of N-acetylcysteine for prevention of thrombotic events after allogenic hematopoietic stem cell transplantation.

Official Title
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The Efficiency and Safety of N-acetylcysteine for Prevention of Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation

Conditions
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Thrombotic Disorder

Intervention / Treatment
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* Drug: N-acetyl-cysteine
* Drug: Busulfan
* Drug: Cytarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 16-70 years old Diagnosed as myeloid malignancies, and about to undergo allo-HSCT; ECOG: 0-2; Expected survival longer than 1 month Exclusion Criteria: Allergic to any components of NAC; Severe dysfunction of heart, liver, lung and kidney; Relapse before HSCT; A history of bronchial asthma, bronchospasm or moderate / severe gastrohelcosis.

Ages Eligible for Study
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Minimum Age: 16 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion; N-acetyl-cysteine (Zambon Pharma, Hainan, China) : 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45. | Drug: N-acetyl-cysteine<br>* 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45<br>* Other names: NAC;Drug: Busulfan<br>* 3.2mg/kg, day-7 to day -5, intravenously<br>* Other names: BU;Drug: Cytarabine<br>* 2g/m2, day -8, intravenously<br>* Other names: Ara-C;Drug: Cyclophosphamide<br>* 1.8g/m2, day -4 to day -3, intravenously<br>* Other names: CTX;|
| Active Comparator: Arm B<br>Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion. | Drug: Busulfan<br>* 3.2mg/kg, day-7 to day -5, intravenously<br>* Other names: BU;Drug: Cytarabine<br>* 2g/m2, day -8, intravenously<br>* Other names: Ara-C;Drug: Cyclophosphamide<br>* 1.8g/m2, day -4 to day -3, intravenously<br>* Other names: CTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of thrombotic disorders | The incidence of thrombotic disorders (TA-TMA, SOS, DVT, PTE, CRT, SVT) after allogenic hematopoietic stem cell transplantation | 1 year | 
| Overall survival | The rate of overall survival after allogenic hematopoietic stem cell transplantation | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of relapse | The incidence of relapse after allogenic hematopoietic stem cell transplantation | 1 year | 
| The incidence of GVHD | The incidence of GVHD after allogenic hematopoietic stem cell transplantation | 1 year | 
| The incidence of hematopoietic reconstitution | The incidence of hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombotic disorder, Hematopoietic stem cell transplantation