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

Soochow University

Status and phase: Not yet enrolling; Phase 3

Conditions: Thrombotic Disorder

Treatments: Drug: Cytarabine; Drug: Cyclophosphamide; Drug: N-acetyl-cysteine; Drug: Busulfan

Study type: Interventional

Funder types: Other

Identifiers

NCT05907486

SOOCHOW-HY-2023-05-30

Details and patient eligibility

About

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

Full 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.

Enrollment: 260 estimated patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 16-70 years old
2. Diagnosed as myeloid malignancies, and about to undergo allo-HSCT;
3. ECOG: 0-2;
4. Expected survival longer than 1 month

Exclusion criteria

1. Allergic to any components of NAC;
2. Severe dysfunction of heart, liver, lung and kidney;
3. Relapse before HSCT;
4. A history of bronchial asthma, bronchospasm or moderate / severe gastrohelcosis.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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260 participants in 2 patient groups

Arm A

Experimental group

Description:

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.

Treatment:

Drug: Busulfan

Drug: Cyclophosphamide

Drug: N-acetyl-cysteine

Drug: Cytarabine

Arm B

Active Comparator group

Description:

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.

Treatment:

Drug: Busulfan

Drug: Cyclophosphamide

Drug: Cytarabine