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

A Phase 3, Randomized, Adaptive Study Comparing the Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant

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.

Study Overview

• Status: Completed
• Conditions: Veno-occlusive Disease
• Intervention / Treatment: Other: Best Supportive Care; Drug: Defibrotide

• Study Type: Interventional
• Enrollment (Actual): 372
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire du Sart Tilman
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Sainte Justine Hospital
• France
  • Besançon, France, 25030
    • Hôpital Jean Minjoz
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Poitiers, France, 86000
    • CHU de Poitiers
  • Toulouse, France
    • Institut Universitaire du Cancer de Toulouse - Oncopole
• Germany
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf
  • Regensburg, Germany, 93053
    • Klinikum der Universität Regensburg
  • Brandenburg
    • Frankfurt (Oder), Brandenburg, Germany, 15236
      • Klinikum Frankfurt Oder GmbH
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Universitatsklinikum der RWTH Aachen
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitatsklinikum Munster
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus an der TU Dresden
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig
• Israel
  • Haifa, Israel, 31999
    • Rambam Health Care Campus
  • Haifa, Israel, 31999
    • Rambam Health Corporation
  • Jerusalem, Israel, 91120
    • Hadassah Ein Kerem Hospital
  • Petaẖ Tiqwa, Israel, 49202
    • Schneider Children Medical Center of Israel
  • Ramat Gan, Israel, 52621
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Ancona, Italy, 60020
    • 11. Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G M Lancisi G Salesi
  • Catania, Italy, 95124
    • Azienda Ospedaliero - Universitaria
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Pesaro, Italy, 61122
    • AORMN Marche Nord
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A Gemelli
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesù
• Japan
  • Anjo, Japan, 446-8602
    • Anjo Kosei Hospital
  • Fukuoka, Japan, 810-8539
    • Hamanomachi Hospital
  • Fukushima, Japan, 960-1247
    • Fukushima Medical University Hospital
  • Hyōgo, Japan, 650-0017
    • Kobe University Hospital
  • Kanagawa, Japan, 232-8555
    • Kanagawa Children's Medical Center
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Nagoya, Japan, 453-0046
    • Japanese Red Cross Nagoya Daiichi Hospital
  • Nishinomiya, Japan, 663-8501
    • Hyogo College of Medicine
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Tokyo, Japan, 105-0001
    • Toranomon Hospital
  • Tokyo, Japan, 113-0021
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Tokyo, Japan, 113-8519
    • Medical Hospital Tokyo Medical and Dental University
• Korea, Republic of
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 6591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital at Yonsei University Health System
• New Zealand
  • Auckland, New Zealand, 1142
    • Auckland City Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d Hebron
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Esplugues de Llobregat, Spain, 8950
    • Hospital Sant Joan de Deu - PIN
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga Hospital General
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol
• Turkey
  • Ankara, Turkey, 06520
    • Medicana International Ankara Hospital
  • Antalya, Turkey, 07160
    • Medical Park Antalya Hospital
  • Bornova, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Istanbul, Turkey, 34303
    • Acibadem Universitesi Tip Fakultesi Atakent Hastanesi
  • Seyhan, Turkey, 1130
    • Acibadem Adana Hospital
  • Konyaalti
    • Antalya, Konyaalti, Turkey, 07070
      • Akdeniz University Medical Faculty Department of Pediatrics
  • Talas
    • Kayseri, Talas, Turkey
      • Erciyes University Medical Faculty
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Glasgow, United Kingdom, G12 0YH
    • Beatson West of Scotland Cancer Centre
  • Glasgow, United Kingdom, G3 8SJ
    • Royal Hospital For Children
  • Leeds, United Kingdom, LS9 7TF
    • St. James University Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92123
      • Rady Childrens Hospital San Diego
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Children's Hospital
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Childrens Hospital
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Childrens Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Tufts Floating Hospital for Children
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10174
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospital Case Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Doernbecher Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - PPDS
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Childrens Hospital
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Texas childrens Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Defibrotide
Other: 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	Other: Best Supportive Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Veno-Occlusive Disease (VOD)-Free Survival by Day +100 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 +100 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +100 post-HSCT.	Day +100 Post-HSCT
Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)	The number of participants who were diagnosed with VOD based on the Modified Seattle Criteria as per blinded EPAC assessment. The percentage was calculated out of the total number of participants in each arm of the study. The values reported below are the numbers and percentages of participants who experienced VOD by Day +30 post-HSCT.	Day +30 Post-HSCT
Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria. An event is defined as a VOD diagnosis or death, whichever, is earlier, up to and including Day +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was based on Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments. The values reported below are participants who did not experience VOD or death by Day +180 post-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)	NRM is defined as death that occurs after HSCT in participants who were noted as having malignant primary disease on the disease history electronic case report form (eCRF) and do not have primary disease relapse post-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	VOD-associated MOD is defined for participants as occurring if the investigator answers "Yes" to the question "Has the participant been diagnosed with VOD associated MOD?" in the electronic case report form (eCRF). The values below are the number of participants who received the answer, "Yes."	Days +30 and +100 Post-HSCT
Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	The proportion of participants who had resolution of VOD by Day +180 post-HSCT is reported as a percentage.	Day +180 Post-HSCT
Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	Time to Resolution of VOD is calculated as follows: Time to Resolution of VOD= [Date of VOD resolution] - [Date of VOD diagnosis by investigator].	Day +180 Post-HSCT
Percentage of Participants With Veno-Occlusive Disease (VOD) After Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) up to Days +100 and +180 Post-HSCT	The values shown are the number and percentage of participants with VOD after day +30 post-HSCT and on or before Days +100 and +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was made by Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments.	Days +100 and +180 Post-HSCT
Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Mobility	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Self-Care	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Activity	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Pain	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Anxiety	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Mobility	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Self-Care	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Activity	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Pain	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Anxiety	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Mobility	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Self-Care	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Activity	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Pain	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Anxiety	For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.	Day +180 Post-HSCT
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase	Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.	Day +1 and +7 Post-HSCT
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase	AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.	Day +1 and +7 Post-HSCT
Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase	Mean systemic clearance after intravenous dosing. Mean clearance is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.	Day +1 and +7 Post-HSCT
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase	Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis.If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.	Day +1 and +7 Post-HSCT
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase	Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.	Day +14 Post-VOD Treatment
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase	AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.	Day +14 Post-VOD Treatment
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase	Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.	Day +14 Post-VOD Treatment
Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Prophylaxis Phase	The number and percentage of participants with Grade 2-4 acute GvHD in the prophylaxis phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.	Days +30, +100, and +180 Post-HSCT
Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Rescue Phase	The number and percentage of participants with Grade 2-4 acute GvHD in the rescue phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.	Days +30, +100, and +180 Post-HSCT
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	The values shown are the number and percentages of participants who developed chronic GvHD by Day +180 post-HSCT in the prophylaxis phase and rescue phase.	Day +180 Post-HSCT
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase	Graft failure is defined as participants that after hematopoietic stem cell transplant (HSCT) never reached an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days or a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination. For the subset of participants who developed VOD and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.	Day +180 Post-HSCT
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	The date of neutrophil engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days. The definition of "absolute neutrophil count" includes both segmented neutrophils and "bands," immature neutrophils. The number of participants with neutrophil engraftment was assessed.	Day +180 Post-HSCT
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	The date of platelet engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. The number of participants with platelet engraftment was assessed.	Day +180 Post-HSCT

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Investigators: Study Director: Jazz Pharmaceuticals, Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): October 20, 2020
• Study Completion (Actual): October 20, 2020

Study Registration Dates

• First Submitted: July 27, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): August 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: stem cell transplant; hematopoietic stem cell transplant (HSCT); veno-occlusive disease (VOD); sinusoidal obstruction syndrome (SOS)
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hepatic Veno-Occlusive Disease; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Defibrotide
• Other Study ID Numbers: 15-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No