Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients

NCT ID: NCT02851407

Last Updated: 2022-03-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

372 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-01

Study Completion Date

2020-10-20

Brief Summary

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This study is to compare the efficacy and safety of defibrotide prophylaxis in addition to best supportive care versus best supportive care alone in the prevention of hepatic veno- occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem cell transplant who are at high risk or very high risk of developing VOD.

Detailed Description

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Conditions

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Veno-occlusive Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Defibrotide

Defibrotide is administered intravenously at a dose of 25 mg/kg/day in addition to best supportive care on the day before the first day of the conditioning regimen and will continue (for those patients without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post HSCT

Group Type EXPERIMENTAL

Defibrotide

Intervention Type DRUG

Best Supportive Care

Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and patient need, is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner, or diagnosis of VOD, if applicable

Group Type OTHER

Best Supportive Care

Intervention Type OTHER

Interventions

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Defibrotide

Intervention Type DRUG

Best Supportive Care

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Patient must be above the age of 1 month as of the start date of study treatment.
2. Patient must be scheduled to undergo allogeneic hematopoietic stem cell transplant (HSCT) (adults or pediatric patients) or autologous HSCT (pediatric patients only) and be at high risk or very high risk of developing veno-occlusive disease (VOD).
3. Female patients (and female partners of male patients) of childbearing potential who are sexually active must agree to use a highly effective method of contraception with their partners during exposure to defibrotide and for 1 week after the last dose of defibrotide.
4. Adult patients must be able to understand and sign a written informed consent. For minor patients, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria

1. Patient has hemodynamic instability within 24 hours before the start of study treatment.
2. Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment.
3. Patient used any medication that increases the risk of bleeding within 24 hours before the start of study treatment.
4. Patient is using or plans to use an investigational agent for the prevention or treatment of VOD.
5. Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
6. Patient or parent/legal guardian or representative has a psychiatric illness that would prevent the patient or parent/legal guardian or representative from giving informed consent and/or assent.
7. 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.
8. Patient is pregnant or lactating and does not agree to stop breastfeeding.
9. Patient has a known history of hypersensitivity to defibrotide or any of the excipients.
10. Patient or parent/legal guardian or representative lacks the full mental capacity to understand and sign a written informed consent.
11. Patient is receiving or plans to receive other investigational therapy during study.
Minimum Eligible Age

1 Month

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jazz Pharmaceuticals

Role: STUDY_DIRECTOR

Jazz Pharmaceuticals

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Rady Childrens Hospital San Diego

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Colorado Children's Hospital

Aurora, Colorado, United States

Site Status

Alfred I Dupont Hospital For Children

Wilmington, Delaware, United States

Site Status

Nicklaus Childrens Hospital

Miami, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

Site Status

Tufts Floating Hospital for Children

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University Hospital Case Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina - PPDS

Charleston, South Carolina, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Children's Medical Center Dallas

Dallas, Texas, United States

Site Status

Cook Childrens Hospital

Fort Worth, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Childrens Hospital

Houston, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Royal Children's Hospital Melbourne

Melbourne, Victoria, Australia

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Universitaire du Sart Tilman

Liège, , Belgium

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

Sainte Justine Hospital

Montreal, Quebec, Canada

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Hopital Jean Minjoz

Besançon, , France

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Institut Paoli Calmettes

Marseille, , France

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Hôpital Saint Antoine

Paris, , France

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CHU de Poitiers

Poitiers, , France

Site Status

Institut Universitaire du Cancer de Toulouse - Oncopôle

Toulouse, , France

Site Status

Klinikum Frankfurt Oder GmbH

Frankfurt (Oder), Brandenburg, Germany

Site Status

Universitätsklinikum der RWTH Aachen

Aachen, North Rhine-Westphalia, Germany

Site Status

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, Germany

Site Status

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Saxony, Germany

Site Status

Universitätsklinikum Leipzig

Leipzig, Saxony, Germany

Site Status

Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Klinikum der Universitat Regensburg

Regensburg, , Germany

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Rambam Health Corporation

Haifa, , Israel

Site Status

Hadassah Ein Kerem Hospital

Jerusalem, , Israel

Site Status

Schneider Children Medical Center of Israel

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

11. Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G M Lancisi G Salesi

Ancona, , Italy

Site Status

Azienda Ospedaliero - Universitaria

Catania, , Italy

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Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

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AORMN Marche Nord

Pesaro, , Italy

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Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Site Status

Fondazione Policlinico Universitario A Gemelli

Roma, , Italy

Site Status

Anjo Kosei Hospital

Anjo, , Japan

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Hamanomachi Hospital

Fukuoka, , Japan

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Fukushima Medical University Hospital

Fukushima, , Japan

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Kobe University Hospital

Hyōgo, , Japan

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Kanagawa Children's Medical Center

Kanagawa, , Japan

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National Hospital Organization Kumamoto Medical Center

Kumamoto, , Japan

Site Status

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, , Japan

Site Status

Hyogo College of Medicine

Nishinomiya, , Japan

Site Status

Osaka International Cancer Institute

Osaka, , Japan

Site Status

Osaka City University Hospital

Osaka, , Japan

Site Status

Hokkaido University Hospital

Sapporo, , Japan

Site Status

Toranomon Hospital

Tokyo, , Japan

Site Status

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Tokyo, , Japan

Site Status

Medical Hospital Tokyo Medical and Dental University

Tokyo, , Japan

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital at Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, , Spain

Site Status

Hospital Infantil Universitario Niño Jesus

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga Hospital General

Málaga, , Spain

Site Status

Hospital General Universitario Morales Meseguer

Murcia, , Spain

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Hospital Universitario de Salamanca

Salamanca, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Akdeniz University Medical Faculty Department of Pediatrics

Antalya, Konyaalti, Turkey (Türkiye)

Site Status

Erciyes University Medical Faculty

Kayseri, Talas, Turkey (Türkiye)

Site Status

Medicana International Ankara Hospital

Ankara, , Turkey (Türkiye)

Site Status

Medical Park Antalya Hospital

Antalya, , Turkey (Türkiye)

Site Status

Ege Universitesi Tip Fakultesi

Bornova, , Turkey (Türkiye)

Site Status

Acibadem Universitesi Tip Fakultesi Atakent Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

Acibadem Adana Hospital

Seyhan, , Turkey (Türkiye)

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Royal Hospital for Children

Glasgow, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Great Ormond Street Hospital

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Israel Italy Japan New Zealand South Korea Spain Turkey (Türkiye) United Kingdom

References

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Corbacioglu S, Grupp SA, Richardson PG, Duarte R, Pagliuca A, Ruutu T, Mahadeo K, Carreras E. Prevention of veno-occlusive disease/sinusoidal obstruction syndrome: a never-ending story and no easy answer. Bone Marrow Transplant. 2023 Aug;58(8):839-841. doi: 10.1038/s41409-023-02007-2. Epub 2023 May 25. No abstract available.

Reference Type DERIVED
PMID: 37231094 (View on PubMed)

Grupp SA, Corbacioglu S, Kang HJ, Teshima T, Khaw SL, Locatelli F, Maertens J, Stelljes M, Stepensky P, Lopez P, Amber V, Pagliuca A, Richardson PG, Mohty M. Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial. Lancet Haematol. 2023 May;10(5):e333-e345. doi: 10.1016/S2352-3026(23)00011-X. Epub 2023 Mar 28.

Reference Type DERIVED
PMID: 37001534 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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15-007

Identifier Type: -

Identifier Source: org_study_id

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