Clinical trial NCT04712435: Efficacy of N-acetylcysteine Versus Placebo as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation
Official title: Prospective, Randomized Study Using N-Acetylcysteine as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sinusoidal Obstruction Syndrome (SOS)
Hematopoietic Stem Cell Transplant (HSCT)
Keywords: Stem cell transplant
Hematopoietic stem cell transplant (HSCT)
Sinusoidal obstruction syndrome (SOS)
Veno-occlusive disease (VOD)
N-acetylcysteine
Lead sponsor: Instituto Brasileiro de Controle do Cancer
Sponsor class: OTHER
First posted: 2021-01-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Presence or absence of SOS
timeFrame: Day + 30 post HSCT
Secondary outcomes:
measure: Severity of SOS
timeFrame: within 30 days of bone marrow transplant
measure: Sinusoidal obstruction syndrome (SOS) -Free Survival at Day 30 Post-Hematopoietic Stem Cell Transplant (HSCT)
timeFrame: 30 Days Post-Transplant
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Jamilla Neves Cavalcante
state: SP
Study officials:
affiliation: IBCC Oncologia
name: Jamilla N Cavalcante, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: Ozdemir ZC, Turhan AB, Eren M, Bor O. 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. No abstract available.
citation: Barkholt L, Remberger M, Hassan Z, Fransson K, Omazic B, Svahn BM, Karlsson H, Brune M, Hassan M, Mattsson J, Ringden 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.
citation: Ringden 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. doi: 10.1038/sj.bmt.1702387.