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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

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

NCT ID

NCT04712435

First Posted

January 13, 2021

Last Updated

March 8, 2021

Sponsor

Instituto Brasileiro de Controle do Cancer

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

Arm Title

Placebo Comparator: Placebo

Arm Type

Placebo Comparator

Arm Description

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

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

millacavalcante@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Alayne D Yamada, PhD

Phone

+55113474-4242

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

ZIP/Postal Code

03102-002

Country

Brazil

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jamilla N Cavalcante, MD

Phone

+55113474-4428

millacavalcante@hotmail.com

First Name & Middle Initial & Last Name & Degree

Alayne D Yamada, PhD

Phone

+55113474-4242

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

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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