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

Primary Purpose

Sinusoidal Obstruction Syndrome (SOS), Hematopoietic Stem Cell Transplant (HSCT)

Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
N-acetylcysteine
Placebo
Sponsored by
Instituto Brasileiro de Controle do Cancer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Sinusoidal Obstruction Syndrome (SOS) focused on measuring Stem cell transplant, Hematopoietic stem cell transplant (HSCT), Sinusoidal obstruction syndrome (SOS), Veno-occlusive disease (VOD), N-acetylcysteine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jamilla Neves Cavalcante

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental: N-acetylcysteine

Placebo Comparator: Placebo

Arm Description

Sachets containing N-acetylcysteine 200 mg Powder for Oral Solution administered every 8 hours (Daily dose 600 mg/day). is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner

200mg granulated solution of matching placebo administered every 8 hours (Daily dose 600 mg/day), is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner

Outcomes

Primary Outcome Measures

Presence or absence of SOS
To evaluate if prophylactic of N-acetylcysteine has an impact on the incidence of Sinusoidal obstruction syndrome (SOS)

Secondary Outcome Measures

Severity of SOS
Death as noted in medical record
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

Full Information

First Posted
January 13, 2021
Last Updated
March 8, 2021
Sponsor
Instituto Brasileiro de Controle do Cancer
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1. Study Identification

Unique Protocol Identification Number
NCT04712435
Brief Title
Efficacy of N-acetylcysteine Versus Placebo as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation
Acronym
ALISON
Official Title
Prospective, Randomized Study Using N-Acetylcysteine as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 2021 (Anticipated)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Brasileiro de Controle do Cancer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine
Masking
ParticipantInvestigator
Masking Description
Matching placebo
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: N-acetylcysteine
Arm Type
Experimental
Arm Description
Sachets containing N-acetylcysteine 200 mg Powder for Oral Solution administered every 8 hours (Daily dose 600 mg/day). is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner
Arm Title
Placebo Comparator: Placebo
Arm Type
Placebo Comparator
Arm Description
200mg granulated solution of matching placebo administered every 8 hours (Daily dose 600 mg/day), is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine
Intervention Description
Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo
Primary Outcome Measure Information:
Title
Presence or absence of SOS
Description
To evaluate if prophylactic of N-acetylcysteine has an impact on the incidence of Sinusoidal obstruction syndrome (SOS)
Time Frame
Day + 30 post HSCT
Secondary Outcome Measure Information:
Title
Severity of SOS
Description
Death as noted in medical record
Time Frame
within 30 days of bone marrow transplant
Title
Sinusoidal obstruction syndrome (SOS) -Free Survival at Day 30 Post-Hematopoietic Stem Cell Transplant (HSCT)
Description
Comparison of efficacy of N-acetylcysteine vs Placebo for the prevention of SOS
Time Frame
30 Days Post-Transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jamilla N Cavalcante, MD
Phone
+55113474-4428
Email
millacavalcante@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Alayne D Yamada, PhD
Phone
+55113474-4242
Email
alayne.pesquisa@ibcc-mooca.org.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jamilla N Cavalcante, MD
Organizational Affiliation
IBCC Oncologia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jamilla Neves Cavalcante
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
03102-002
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jamilla N Cavalcante, MD
Phone
+55113474-4428
Email
millacavalcante@hotmail.com
First Name & Middle Initial & Last Name & Degree
Alayne D Yamada, PhD
Phone
+55113474-4242
Email
alayne.pesquisa@ibcc-mooca.org.br
First Name & Middle Initial & Last Name & Degree
Jamilla N Cavalcante, MD
First Name & Middle Initial & Last Name & Degree
Maria Cristina M Macedo, PhD
First Name & Middle Initial & Last Name & Degree
Larissa Y Okada, MD
First Name & Middle Initial & Last Name & Degree
Lauro Augusto C Leite, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24102514
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.
Results Reference
background
PubMed Identifier
25798682
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.
Results Reference
background
PubMed Identifier
26431626
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.
Results Reference
background
PubMed Identifier
28401107
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.
Results Reference
background
PubMed Identifier
18176610
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.
Results Reference
background
PubMed Identifier
10800069
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.
Results Reference
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Efficacy of N-acetylcysteine Versus Placebo as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation

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