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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02851407




Registration number
NCT02851407
Ethics application status
Date submitted
27/07/2016
Date registered
1/08/2016

Titles & IDs
Public title
Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients
Scientific title
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
Secondary ID [1] 0 0
15-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Veno-occlusive Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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

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

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
Timepoint [1] 0 0
Day +30 Post-HSCT
Secondary outcome [1] 0 0
Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
Timepoint [1] 0 0
Day +100 Post-HSCT
Secondary outcome [2] 0 0
Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [2] 0 0
Day +30 Post-HSCT
Secondary outcome [3] 0 0
Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [3] 0 0
Day +180 Post-HSCT
Secondary outcome [4] 0 0
Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [4] 0 0
Days +100 and +180 Post-HSCT
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Days +30 and +100 Post-HSCT
Secondary outcome [6] 0 0
Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [6] 0 0
Day +180 Post-HSCT
Secondary outcome [7] 0 0
Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [7] 0 0
Day +180 Post-HSCT
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Days +100 and +180 Post-HSCT
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Day +180 Post-HSCT
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Day +180 Post-HSCT
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Day +180 Post-HSCT
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Day +180 Post-HSCT
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Day +180 Post-HSCT
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Day +180 Post-HSCT
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Day +180 Post-HSCT
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Day +180 Post-HSCT
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
Day +180 Post-HSCT
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
Day +180 Post-HSCT
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
Day +180 Post-HSCT
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
Day +180 Post-HSCT
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
Day +180 Post-HSCT
Secondary outcome [22] 0 0
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
Timepoint [22] 0 0
Day +180 Post-HSCT
Secondary outcome [23] 0 0
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
Timepoint [23] 0 0
Day +180 Post-HSCT
Secondary outcome [24] 0 0
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase
Timepoint [24] 0 0
Day +1 and +7 Post-HSCT
Secondary outcome [25] 0 0
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase
Timepoint [25] 0 0
Day +1 and +7 Post-HSCT
Secondary outcome [26] 0 0
Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase
Timepoint [26] 0 0
Day +1 and +7 Post-HSCT
Secondary outcome [27] 0 0
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase
Timepoint [27] 0 0
Day +1 and +7 Post-HSCT
Secondary outcome [28] 0 0
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase
Timepoint [28] 0 0
Day +14 Post-VOD Treatment
Secondary outcome [29] 0 0
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase
Timepoint [29] 0 0
Day +14 Post-VOD Treatment
Secondary outcome [30] 0 0
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase
Timepoint [30] 0 0
Day +14 Post-VOD Treatment
Secondary outcome [31] 0 0
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
Timepoint [31] 0 0
Days +30, +100, and +180 Post-HSCT
Secondary outcome [32] 0 0
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
Timepoint [32] 0 0
Days +30, +100, and +180 Post-HSCT
Secondary outcome [33] 0 0
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [33] 0 0
Day +180 Post-HSCT
Secondary outcome [34] 0 0
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase
Timepoint [34] 0 0
Day +180 Post-HSCT
Secondary outcome [35] 0 0
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [35] 0 0
Day +180 Post-HSCT
Secondary outcome [36] 0 0
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [36] 0 0
Day +180 Post-HSCT

Eligibility
Key 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.
Minimum age
1 Month
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Children's Hospital Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Belgium
State/province [23] 0 0
Bruxelles
Country [24] 0 0
Belgium
State/province [24] 0 0
Gent
Country [25] 0 0
Belgium
State/province [25] 0 0
Leuven
Country [26] 0 0
Belgium
State/province [26] 0 0
Liege
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
France
State/province [29] 0 0
Besançon
Country [30] 0 0
France
State/province [30] 0 0
Marseille
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Poitiers
Country [33] 0 0
France
State/province [33] 0 0
Toulouse
Country [34] 0 0
Germany
State/province [34] 0 0
Brandenburg
Country [35] 0 0
Germany
State/province [35] 0 0
Nordrhein-Westfalen
Country [36] 0 0
Germany
State/province [36] 0 0
Sachsen
Country [37] 0 0
Germany
State/province [37] 0 0
Hamburg
Country [38] 0 0
Germany
State/province [38] 0 0
Regensburg
Country [39] 0 0
Israel
State/province [39] 0 0
Haifa
Country [40] 0 0
Israel
State/province [40] 0 0
Jerusalem
Country [41] 0 0
Israel
State/province [41] 0 0
Peta? Tiqwa
Country [42] 0 0
Israel
State/province [42] 0 0
Ramat Gan
Country [43] 0 0
Israel
State/province [43] 0 0
Tel Aviv
Country [44] 0 0
Italy
State/province [44] 0 0
Ancona
Country [45] 0 0
Italy
State/province [45] 0 0
Catania
Country [46] 0 0
Italy
State/province [46] 0 0
Firenze
Country [47] 0 0
Italy
State/province [47] 0 0
Pesaro
Country [48] 0 0
Italy
State/province [48] 0 0
Roma
Country [49] 0 0
Japan
State/province [49] 0 0
Anjo
Country [50] 0 0
Japan
State/province [50] 0 0
Fukuoka
Country [51] 0 0
Japan
State/province [51] 0 0
Fukushima
Country [52] 0 0
Japan
State/province [52] 0 0
Hyogo
Country [53] 0 0
Japan
State/province [53] 0 0
Kanagawa
Country [54] 0 0
Japan
State/province [54] 0 0
Kumamoto
Country [55] 0 0
Japan
State/province [55] 0 0
Nagoya
Country [56] 0 0
Japan
State/province [56] 0 0
Nishinomiya
Country [57] 0 0
Japan
State/province [57] 0 0
Osaka
Country [58] 0 0
Japan
State/province [58] 0 0
Sapporo
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo
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Korea, Republic of
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Seoul
Country [61] 0 0
New Zealand
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Auckland
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Cordoba
Country [64] 0 0
Spain
State/province [64] 0 0
Esplugues de Llobregat
Country [65] 0 0
Spain
State/province [65] 0 0
Madrid
Country [66] 0 0
Spain
State/province [66] 0 0
Malaga
Country [67] 0 0
Spain
State/province [67] 0 0
Murcia
Country [68] 0 0
Spain
State/province [68] 0 0
Salamanca
Country [69] 0 0
Spain
State/province [69] 0 0
Sevilla
Country [70] 0 0
Turkey
State/province [70] 0 0
Konyaalti
Country [71] 0 0
Turkey
State/province [71] 0 0
Talas
Country [72] 0 0
Turkey
State/province [72] 0 0
Ankara
Country [73] 0 0
Turkey
State/province [73] 0 0
Antalya
Country [74] 0 0
Turkey
State/province [74] 0 0
Bornova
Country [75] 0 0
Turkey
State/province [75] 0 0
Istanbul
Country [76] 0 0
Turkey
State/province [76] 0 0
Seyhan
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Birmingham
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Glasgow
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Leeds
Country [80] 0 0
United Kingdom
State/province [80] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Jazz Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jazz Pharmaceuticals
Address 0 0
Jazz Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.