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

Phase 3

Not yet recruiting

• Conditions: Thrombotic Disorder
• Interventions: Drug: Busulfan; Drug: N-acetyl-cysteine; Drug: Cyclophosphamide; Drug: Cytarabine

• Registration Number: NCT05907486
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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.

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 Timeline

• Status Verified: 2023-05
• Study First Submitted: 2023-06-08
• Study First Submitted QC: 2023-06-08
• Last Update Submitted: 2023-06-08
• Study First Posted: 2023-06-18
• Last Update Posted: 2023-06-18
• Study Start: 2023-08-01
• Primary Completion: 2025-08-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 260

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Busulfan	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.
Arm B	Cyclophosphamide	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.
Arm A	N-acetyl-cysteine	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.
Arm A	Cytarabine	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.
Arm B	Cytarabine	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.
Arm A	Cyclophosphamide	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.
Arm A	Busulfan	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
The incidence of GVHD	1 year	The incidence of GVHD after allogenic hematopoietic stem cell transplantation
The incidence of relapse	1 year	The incidence of relapse after allogenic hematopoietic stem cell transplantation
The incidence of hematopoietic reconstitution	1 year	The incidence of hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation