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

NCT05907486 | Unknown Phase 3 DMC

• 1 other identifier: SOOCHOW-HY-2023-05-30
• Study Type: interventional
• Target: 260
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Thrombotic Disorder

Keywords

Thrombotic disorder; Hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• The incidence of relapse

  1 year

• The incidence of GVHD

  1 year

• The incidence of hematopoietic reconstitution

  1 year

Study Arms (2)

Arm A

EXPERIMENTAL

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; Drug: Busulfan; Drug: Cytarabine; Drug: Cyclophosphamide

Arm B

ACTIVE COMPARATOR

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; Drug: Cytarabine; Drug: Cyclophosphamide

Interventions

N-acetyl-cysteine DRUG

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

Also known as: NAC

Arm A

Busulfan DRUG

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

Also known as: BU

Arm A; Arm B

Cytarabine DRUG

2g/m2, day -8, intravenously

Also known as: Ara-C

Arm A; Arm B

Cyclophosphamide DRUG

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

Also known as: CTX

Arm A; Arm B

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Related Publications (9)

• Labrador J, Lopez-Anglada L, Perez-Lopez E, Lozano FS, Lopez-Corral L, Sanchez-Guijo FM, Vazquez L, Perez Rivera JA, Martin-Herrero F, Sanchez-Barba M, Guerrero C, del Canizo MC, Caballero MD, San Miguel JF, Alberca I, Gonzalez-Porras JR. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients. Haematologica. 2013 Mar;98(3):437-43. doi: 10.3324/haematol.2012.069559. Epub 2012 Aug 16.

  PMID: 22899581 BACKGROUND

• Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011 Aug 11;118(6):1452-62. doi: 10.1182/blood-2011-02-321315. Epub 2011 May 19.

  PMID: 21596850 BACKGROUND

• George JN, Li X, McMinn JR, Terrell DR, Vesely SK, Selby GB. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. 2004 Feb;44(2):294-304. doi: 10.1111/j.1537-2995.2004.00700.x.

  PMID: 14962323 BACKGROUND

• Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010 Feb;16(2):157-68. doi: 10.1016/j.bbmt.2009.08.024. Epub 2009 Sep 18.

  PMID: 19766729 BACKGROUND

• Tsirigotis PD, Resnick IB, Avni B, Grisariu S, Stepensky P, Or R, Shapira MY. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen. Bone Marrow Transplant. 2014 Nov;49(11):1389-92. doi: 10.1038/bmt.2014.168. Epub 2014 Jul 28.

  PMID: 25068424 BACKGROUND

• Carreras E, Diaz-Beya M, Rosinol L, Martinez C, Fernandez-Aviles F, Rovira M. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant. 2011 Nov;17(11):1713-20. doi: 10.1016/j.bbmt.2011.06.006. Epub 2011 Jun 25.

  PMID: 21708110 BACKGROUND

• Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM, Goebel J, Dixon BP. A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015 May;29(3):191-204. doi: 10.1016/j.blre.2014.11.001. Epub 2014 Nov 28.

  PMID: 25483393 BACKGROUND

• Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M, Ferrara J, Soiffer R, Giralt S. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005 Aug;11(8):571-5. doi: 10.1016/j.bbmt.2005.06.001.

  PMID: 16041306 BACKGROUND

• Sartain S, Shubert S, Wu MF, Srivaths P, Teruya J, Krance R, Martinez C. Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy: An Institutional Experience. Biol Blood Marrow Transplant. 2019 Jan;25(1):157-162. doi: 10.1016/j.bbmt.2018.08.016. Epub 2018 Aug 23.

  PMID: 30144562 BACKGROUND

MeSH Terms

Conditions

Thrombosis

Interventions

Acetylcysteine; Busulfan; Cytarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yue Han, Professor

  The First Affiliated Hospital of Soochow University

  STUDY CHAIR

Central Study Contacts

Yaqiong Tang, Doctor

CONTACT

18896588075; tangyaqiong@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: June 18, 2023
• Study Start: August 1, 2023
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share