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

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05907486

Collaborator

(none)

260

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Thrombotic Disorder	Drug: N-acetyl-cysteine Drug: Busulfan Drug: Cytarabine Drug: Cyclophosphamide	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A 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 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45 Other Names: NAC Drug: Busulfan 3.2mg/kg, day-7 to day -5, intravenously Other Names: BU Drug: Cytarabine 2g/m2, day -8, intravenously Other Names: Ara-C Drug: Cyclophosphamide 1.8g/m2, day -4 to day -3, intravenously Other Names: CTX
Active Comparator: Arm B 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 3.2mg/kg, day-7 to day -5, intravenously Other Names: BU Drug: Cytarabine 2g/m2, day -8, intravenously Other Names: Ara-C Drug: Cyclophosphamide 1.8g/m2, day -4 to day -3, intravenously Other Names: CTX

Arm

Intervention/Treatment

Experimental: Arm A

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

8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45

Other Names:

NAC

Drug: Busulfan

3.2mg/kg, day-7 to day -5, intravenously

Other Names:

Drug: Cytarabine

2g/m2, day -8, intravenously

Other Names:

Ara-C

Drug: Cyclophosphamide

1.8g/m2, day -4 to day -3, intravenously

Other Names:

CTX

Active Comparator: Arm B

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

3.2mg/kg, day-7 to day -5, intravenously

Other Names:

Drug: Cytarabine

2g/m2, day -8, intravenously

Other Names:

Ara-C

Drug: Cyclophosphamide

1.8g/m2, day -4 to day -3, intravenously

Other Names:

CTX

Outcome Measures

Primary Outcome Measures

The incidence of thrombotic disorders [1 year]
The incidence of thrombotic disorders (TA-TMA, SOS, DVT, PTE, CRT, SVT) after allogenic hematopoietic stem cell transplantation
Overall survival [1 year]
The rate of overall survival after allogenic hematopoietic stem cell transplantation

Secondary Outcome Measures

The incidence of relapse [1 year]
The incidence of relapse after allogenic hematopoietic stem cell transplantation
The incidence of GVHD [1 year]
The incidence of GVHD after allogenic hematopoietic stem cell transplantation
The incidence of hematopoietic reconstitution [1 year]
The incidence of hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.