Efficacy of N-acetylcysteine Versus Placebo as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplant (HSCT) Clinical Trial

— ALISON  

Official title:

Prospective, Randomized Study Using N-Acetylcysteine as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04712435
• Other study ID #: 33788420.4.0000.0072
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: January 2021
• Source: Instituto Brasileiro de Controle do Cancer
• Contact: Jamilla N Cavalcante, MD
• Phone: +55113474-4428
• Email: millacavalcante[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sinusoidal obstruction syndrome (SOS) or hepatic veno-occlusive disease (VOD) is a serious complication that occurs, most often occurring in patients undergoing hematopoietic stem cell transplantation (HSCT), especially in its first thirty days. The morbidity and mortality in this syndrome are considerable, since severe SOS is associated with a mortality of more than 90% in the first hundred days of HSCT. Some risk factors are modifiable, especially those related to transplantation, but when non-alterable factors are present, preventive measures are needed that can reduce the incidence and / or severity of SOS.

Description:

This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine as prophylaxis of sinusoidal obstruction syndrome in patients undergoing hematopoietic stem cell transplantation Up to date, no approved medications are available for prophylactic treatment of sinusoidal obstruction syndrome in patients undergoing hematopoietic stem cell transplantation. N-acetylcysteine is a drug that has been long used as a mucolytic. And placebo responses contribute to help assess the appropriateness of randomized clinical trials in determining the size of drug effect. The study will enroll patients undergoing hematopoietic stem cell transplantation to receive sequentially one of two treatment: N-acetylcysteine or Placebo.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men or women
• Age = 18 years
• A proven diagnosis of one of the hematological malignancies: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Chronic Myeloid Leukemia, Chronic Lymphoid Leukemia, Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma
• Patients must be scheduled to undergo of Allogeneic hematopoietic transplantation or HLA (Human Leukocyte Antigen) haploidentical related or Unrelated or HLA-matched related or autologous stem cell transplant
• Patients must be able to understand and sign a written informed consent

Exclusion Criteria:

• Patient has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study
• Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• Known hypersensitivity to N-acetylcysteine
• Contraindications to perform any procedure provided for in this study
• Patients who have already undergone a previous transplant

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant (HSCT)
• Hepatic Veno-Occlusive Disease
• Sinusoidal Obstruction Syndrome (SOS)
• Syndrome

Intervention

Drug:
• N-acetylcysteine
Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo
• Placebo
Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo

Locations

Country	Name	City	State
Brazil	Jamilla Neves Cavalcante	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Brasileiro de Controle do Cancer

Country where clinical trial is conducted

Brazil, 

References & Publications (6)

Barkholt L, Remberger M, Hassan Z, Fransson K, Omazic B, Svahn BM, Karlsson H, Brune M, Hassan M, Mattsson J, Ringdén O. A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008 May;41(9):785-90. doi: 10.1038/sj.bmt.1705969. Epub 2008 Jan 7. — View Citation

Dalle JH, Giralt SA. Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment. Biol Blood Marrow Transplant. 2016 Mar;22(3):400-9. doi: 10.1016/j.bbmt.2015.09.024. Epub 2015 Oct 23. Review. — View Citation

Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 2013 Nov;163(4):444-57. doi: 10.1111/bjh.12558. Epub 2013 Sep 17. — View Citation

Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Ciceri F, Corbacioglu S, Dalle JH, Duarte RF, Fukuda T, Huynh A, Masszi T, Michallet M, Nagler A, NiChonghaile M, Pagluica T, Peters C, Petersen FB, Richardson PG, Ruutu T, Savani BN, Wallhult E, Yakoub-Agha I, Carreras E. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015 Jun;50(6):781-9. doi: 10.1038/bmt.2015.52. Epub 2015 Mar 23. Review. — View Citation

Özdemir ZC, Turhan AB, Eren M, Bor Ö. Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity? Blood Res. 2017 Mar;52(1):69-71. doi: 10.5045/br.2017.52.1.69. Epub 2017 Mar 27. — View Citation

Ringdén O, Remberger M, Lehmann S, Hentschke P, Mattsson J, Klaesson S, Aschan J. N-acetylcysteine for hepatic veno-occlusive disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2000 May;25(9):993-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence or absence of SOS	To evaluate if prophylactic of N-acetylcysteine has an impact on the incidence of Sinusoidal obstruction syndrome (SOS)	Day + 30 post HSCT
Secondary	Severity of SOS	Death as noted in medical record	within 30 days of bone marrow transplant
Secondary	Sinusoidal obstruction syndrome (SOS) -Free Survival at Day 30 Post-Hematopoietic Stem Cell Transplant (HSCT)	Comparison of efficacy of N-acetylcysteine vs Placebo for the prevention of SOS	30 Days Post-Transplant