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

NCT02851407 | Completed Phase 3 Results DMC

• 1 other identifier: 15-007
• Study Type: interventional
• Target: 372
• Locations: 14 countries
• Sites: 114

Brief Summary

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.

Conditions

Veno-occlusive Disease

Keywords

stem cell transplant; hematopoietic stem cell transplant (HSCT); veno-occlusive disease (VOD); sinusoidal obstruction syndrome (SOS)

Outcome Measures

Primary Outcomes (1)

• Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)

  VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +30 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +30 post-HSCT.

  Day +30 Post-HSCT

Secondary Outcomes (36)

• Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)

  Day +100 Post-HSCT

• Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)

  Day +30 Post-HSCT

• Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)

  Day +180 Post-HSCT

• Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT)

  Days +100 and +180 Post-HSCT

• Percentage of Participants With Veno-Occlusive Disease (VOD)-Associated Multi-Organ Dysfunction (MOD) by Days +30 and Days +100 Post-Hematopoietic Stem Cell Transplant (HSCT) in Patients Who Developed VOD

  Days +30 and +100 Post-HSCT

Study Arms (2)

Defibrotide

EXPERIMENTAL

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

Drug: Defibrotide

Best Supportive Care

OTHER

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

Other: Best Supportive Care

Interventions

Defibrotide DRUG

Defibrotide

Best Supportive Care OTHER

Best Supportive Care

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be above the age of 1 month as of the start date of study treatment.
• 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).
• 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.
• 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.

You may not qualify if:

• Patient has hemodynamic instability within 24 hours before the start of study treatment.
• Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment.
• Patient used any medication that increases the risk of bleeding within 24 hours before the start of study treatment.
• Patient is using or plans to use an investigational agent for the prevention or treatment of VOD.
• Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• 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.
• 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 is pregnant or lactating and does not agree to stop breastfeeding.
• Patient has a known history of hypersensitivity to defibrotide or any of the excipients.
• Patient or parent/legal guardian or representative lacks the full mental capacity to understand and sign a written informed consent.
• Patient is receiving or plans to receive other investigational therapy during study.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (114)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Rady Childrens Hospital San Diego

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

Location

Alfred I Dupont Hospital For Children

Wilmington, Delaware, 19803, United States

Location

Nicklaus Childrens Hospital

Miami, Florida, 33155, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Tufts Floating Hospital for Children

Boston, Massachusetts, 02111, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10174, United States

Location

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospital Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Cook Childrens Hospital

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Children's Hospital Melbourne

Melbourne, Victoria, 3052, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire du Sart Tilman

Liège, 4000, Belgium

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Sainte Justine Hospital

Montreal, Quebec, H3T 1C5, Canada

Location

Hopital Jean Minjoz

Besançon, 25030, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopôle

Toulouse, France

Location

Klinikum Frankfurt Oder GmbH

Frankfurt (Oder), Brandenburg, 15236, Germany

Location

Universitätsklinikum der RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Klinikum der Universitat Regensburg

Regensburg, 93053, Germany

Location

Rambam Health Care Campus

Haifa, 31999, Israel

Location

Rambam Health Corporation

Haifa, 31999, Israel

Location

Hadassah Ein Kerem Hospital

Jerusalem, 91120, Israel

Location

Schneider Children Medical Center of Israel

Petah Tikva, 49202, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

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

Ancona, 60020, Italy

Location

Azienda Ospedaliero - Universitaria

Catania, 95124, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

AORMN Marche Nord

Pesaro, 61122, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Roma, 00168, Italy

Location

Anjo Kosei Hospital

Anjo, 446-8602, Japan

Location

Hamanomachi Hospital

Fukuoka, 810-8539, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1247, Japan

Location

Kobe University Hospital

Hyōgo, 650-0017, Japan

Location

Kanagawa Children's Medical Center

Kanagawa, 232-8555, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, 860-0008, Japan

Location

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, 453-0046, Japan

Location

Hyogo College of Medicine

Nishinomiya, 663-8501, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Osaka City University Hospital

Osaka, 545-8586, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Toranomon Hospital

Tokyo, 105-0001, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Tokyo, 113-0021, Japan

Location

Medical Hospital Tokyo Medical and Dental University

Tokyo, 113-8519, Japan

Location

Auckland City Hospital

Auckland, 1142, New Zealand

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Severance Hospital at Yonsei University Health System

Seoul, 3722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

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

Seoul, 6591, South Korea

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Vall d Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, 8950, Spain

Location

Hospital Infantil Universitario Niño Jesus

Madrid, 28009, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Malaga Hospital General

Málaga, 29010, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Akdeniz University Medical Faculty Department of Pediatrics

Antalya, Konyaalti, 07070, Turkey (Türkiye)

Location

Erciyes University Medical Faculty

Kayseri, Talas, Turkey (Türkiye)

Location

Medicana International Ankara Hospital

Ankara, 06520, Turkey (Türkiye)

Location

Medical Park Antalya Hospital

Antalya, 07160, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Bornova, 35100, Turkey (Türkiye)

Location

Acibadem Universitesi Tip Fakultesi Atakent Hastanesi

Istanbul, 34303, Turkey (Türkiye)

Location

Acibadem Adana Hospital

Seyhan, 1130, Turkey (Türkiye)

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YH, United Kingdom

Location

Royal Hospital for Children

Glasgow, G3 8SJ, United Kingdom

Location

St. James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37231094 DERIVED

• 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.

  PMID: 37001534 DERIVED

MeSH Terms

Conditions

Hepatic Veno-Occlusive Disease

Interventions

defibrotide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Director, Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-870-9177

Study Officials

• Jazz Pharmaceuticals

  Jazz Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 1, 2016
• Study Start: September 1, 2016
• Primary Completion: October 20, 2020
• Study Completion: October 20, 2020
• Last Updated: March 2, 2022
• Results First Posted: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); CA (2); IL (6); FR (5); DE (7); TU (7); JP (14); NZ (1); IT (6); KR (5); ES (11); BE (5); AU (2); US (37)