CompletedNCT02851407Updated Mar 2, 2022Results posted

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 interventional study of Defibrotide and Best Supportive Care in Veno-occlusive Disease, sponsored by Jazz Pharmaceuticals. Completed at 114 sites in 14 countries. Open to participants aged 1 Month and older. Per ClinicalTrials.gov, last updated 2022-03-02.

Sponsored by Jazz Pharmaceuticals · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 372
Allocation: Randomized
Ages: 1 Month and older
Sex: All

Study 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 studied

Veno-occlusive Disease

Browse trials for

Hepatic Veno-Occlusive Disease 23

Keywords

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

In context

Hepatic Veno-Occlusive Disease

23 studies on the registry are indexed under Hepatic Veno-Occlusive Disease; 3 are open to participants now.

This study's enrollment of 372 is above the median of 80 across 15 interventional studies indexed under Hepatic Veno-Occlusive Disease.

Browse Hepatic Veno-Occlusive Disease studies →

Lead sponsor

Jazz Pharmaceuticals is the lead sponsor of 167 studies on the registry; 20 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 1 Month and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 372 participants (actual)

Study arms

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

Interventions

DrugDefibrotide
OtherBest Supportive Care

What researchers measure

Primary outcomes

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.
Time frame: Day +30 Post-HSCT

Secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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."
Time frame: 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.
Time frame: 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= \[Date of VOD resolution\] - \[Date of VOD diagnosis by investigator\].
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day +180 Post-HSCT

Results

Posted Mar 2, 2022

Participant flow

Participant flow — Overall Study
Milestone	Defibrotide Prophylaxis	Best Supportive Care
Started	190	182
Completed	120	121
Not completed	70	61
Withdrew: Withdrawal by parent/guardian	2	7
Withdrew: Protocol deviation	0	1
Withdrew: Transferred to another hospital to continue	1	0
Withdrew: Other death	30	20
Withdrew: Adverse event, serious fatal	6	8
Withdrew: Consent withdrawn by participant	5	3
Withdrew: Screen failure	2	1
Withdrew: Disease relapse	9	6
Withdrew: Physician decision	7	6
Withdrew: Transferred to hospital closer to home	0	1
Withdrew: Enrolled in an investigational study	0	1
Withdrew: Early recovery	1	0
Withdrew: Adverse event, non-fatal	7	5
Withdrew: Lost to follow-up	0	2

Outcome measures

PrimaryVeno-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.

Time frame:: Day +30 Post-HSCT
Reported as:: Number · KM Estimate % of participants

Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
KM Estimate % of participants	Defibrotide Prophylaxis	Best Supportive Care
Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)	66.8 (57.8 to 74.4)	72.5 (62.3 to 80.4)

SecondaryVeno-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.

Time frame:: Day +100 Post-HSCT
Reported as:: Number · KM Estimate % of participants

Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
KM Estimate % of participants	Defibrotide Prophylaxis	Best Supportive Care
Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)	49.8 (26.1 to 69.5)	57.1 (36.6 to 73.1)

SecondaryPercentage 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.

Time frame:: Day +30 Post-HSCT
Reported as:: Count of participants · Participants

Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)
Participants	Defibrotide Prophylaxis	Best Supportive Care
Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)	47	38

SecondaryVeno-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.

Time frame:: Day +180 Post-HSCT
Reported as:: Number · KM Estimate % of participants

Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
KM Estimate % of participants	Defibrotide Prophylaxis	Best Supportive Care
Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	34.6 (18.2 to 51.8)	42.8 (26.7 to 58.0)

SecondaryNon-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.

Time frame:: Days +100 and +180 Post-HSCT
Reported as:: Number · KM Estimate % of non-relapse survival

Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
KM Estimate % of non-relapse survival	Defibrotide Prophylaxis	Best Supportive Care
Day +100 Post-HSCT	80.4 (71.6 to 86.8)	89.7 (82.1 to 94.2)
Day +180 Post-HSCT	77.9 (68.4 to 84.9)	81.9 (70.8 to 89.1)

SecondaryPercentage 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."

Time frame:: Days +30 and +100 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Day +30 Post-HSCT	8	8
Day +100 Post-HSCT	9	10

SecondaryPercentage 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Participants	Defibrotide Prophylaxis	Best Supportive Care
Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	6	15

SecondaryTime 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= \[Date of VOD resolution\] - \[Date of VOD diagnosis by investigator\].

Time frame:: Day +180 Post-HSCT
Reported as:: Median · Days

Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Days	Defibrotide Prophylaxis	Best Supportive Care
Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	NA (NA to NA)	30.0 (21.0 to 48.0)

SecondaryPercentage 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.

Time frame:: Days +100 and +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Day +100 Post-HSCT	6	5
Day +180 Post-HSCT	6	5

SecondaryChange 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	4	7
Condition unchaged	28	28
Condition deteriorated	9	6
Unknown	4	5

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	3	6
Condition unchaged	35	32
Condition deteriorated	3	4
Unknown	4	4

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	7	10
Condition unchaged	24	22
Condition deteriorated	9	10
Unknown	5	4

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	10	11
Condition unchaged	25	19
Condition deteriorated	6	12
Unknown	4	4

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	11	11
Condition unchaged	22	27
Condition deteriorated	7	4
Unknown	5	4

SecondaryChange 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	2	1
Condition unchanged	8	8
Condition deteriorated	3	4
Unknown	2	2

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	3	2
Condition unchanged	7	10
Condition deteriorated	3	1
Unknown	2	2

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	2	1
Condition unchanged	7	11
Condition deteriorated	4	1
Unknown	2	2

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	4	3
Condition unchanged	7	9
Condition deteriorated	2	1
Unknown	2	2

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	3	2
Condition unchanged	8	10
Condition deteriorated	2	1
Unknown	2	2

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	1	2
Condition unchanged	9	10
Condition deteriorated	3	4
unknown	1	1

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	3	4
Condition unchanged	8	10
Condition deteriorated	2	2
Unknown	1	1

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	1	3
Condition unchanged	7	10
Condition deteriorated	5	3
Unknown	1	1

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	0	5
Condition unchanged	12	8
Condition deteriorated	1	3
Unknown	1	1

SecondaryChange 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

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Condition improved	6	6
Condition unchanged	5	8
Condition deteriorated	2	2
Unknown	1	1

SecondaryMaximum 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.

Time frame:: Day +1 and +7 Post-HSCT
Reported as:: Mean · μg/mL

Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase
μg/mL	Defibrotide Prophylaxis	Best Supportive Care
Day +1 Post-HSCT	30.4 ± 10.600	—
Day +7 Post-HSCT	40 ± 3.168	—

SecondaryArea 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.

Time frame:: Day +1 and +7 Post-HSCT
Reported as:: Mean · h*μg/mL

Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase
h*μg/mL	Defibrotide Prophylaxis	Best Supportive Care
Day +1 Post-HSCT	61.6 ± 28.488	—
Day +7 Post-HSCT	78.2 ± 10.781	—

SecondaryMean 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.

Time frame:: Day +1 and +7 Post-HSCT
Reported as:: Mean · L/h

Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase
L/h	Defibrotide Prophylaxis	Best Supportive Care
Day +1 Post-HSCT	4.7 ± 0.304	—

SecondaryVolume 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.

Time frame:: Day +1 and +7 Post-HSCT
Reported as:: Mean · L

Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase
L	Defibrotide Prophylaxis	Best Supportive Care
Day +1 Post-HSCT	7.9 ± 0.689	—
Day +7 Post-HSCT	5.9 ± 1.609	—

SecondaryMaximum 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.

Time frame:: Day +14 Post-VOD Treatment
Reported as:: Mean · μg/mL

Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase
μg/mL	Defibrotide Prophylaxis	Best Supportive Care
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase	44.4 ± 18.550	39.7 ± 25.775

SecondaryArea 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.

Time frame:: Day +14 Post-VOD Treatment
Reported as:: Mean · h*μg/mL

Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase
h*μg/mL	Defibrotide Prophylaxis	Best Supportive Care
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase	119.1 ± 68.875	90.7 ± 54.798

SecondaryVolume 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.

Time frame:: Day +14 Post-VOD Treatment
Reported as:: Mean · L

Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase
L	Defibrotide Prophylaxis	Best Supportive Care
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase	6.3 ± 0.654	6.7 ± 5.895

SecondaryPercentage 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.

Time frame:: Days +30, +100, and +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Day +30 Post-HSCT	13	13
Day +100 Post-HSCT	20	24
Day +180 Post-HSCT	22	26

SecondaryPercentage 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.

Time frame:: Days +30, +100, and +180 Post-HSCT
Reported as:: Count of participants · Participants

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
Participants	Defibrotide Prophylaxis	Best Supportive Care
Day +30 Post-HSCT	5	1
Day +100 Post-HSCT	6	1
Day +180 Post-HSCT	6	1

SecondaryPercentage 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Participants	Defibrotide Prophylaxis	Best Supportive Care
Prophylaxis Phase	14	12
Rescue Phase	2	1

SecondaryNumber 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase
Participants	Defibrotide Prophylaxis	Best Supportive Care
Prophylaxis Phase	4	5
Rescue Phase	4	4

SecondaryNumber 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Participants	Defibrotide Prophylaxis	Best Supportive Care
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	156	162

SecondaryNumber 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.

Time frame:: Day +180 Post-HSCT
Reported as:: Count of participants · Participants

Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Participants	Defibrotide Prophylaxis	Best Supportive Care
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	154	163

Adverse events

Collected over Adverse Events (AEs) were reported from the date of consent through Day +180 post-HSCT/Study Completion or Early Termination, or up to 4 years, 1 month.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Defibrotide Prophylaxis	35/181 (19.3%)	82/181 (45.3%)	180/181 (99.4%)
Best Supportive Care	29/174 (16.7%)	74/174 (42.5%)	174/174 (100%)

Most frequent serious events

Showing 10 of 151

Most frequent serious events
Event	Defibrotide Prophylaxis	Best Supportive Care
PyrexiaGastrointestinal disorders	10/181	14/174
Venoocclusive diseaseVascular disorders	9/181	5/174
Respiratory failureRespiratory, thoracic and mediastinal disorders	6/181	6/174
SepsisInfections and infestations	6/181	5/174
DiarrhoeaGastrointestinal disorders	0/181	5/174
Acute graft versus host disease in intestineImmune system disorders	3/181	4/174
Venoocclusive liver diseaseHepatobiliary disorders	2/181	4/174
Acute kidney injuryRenal and urinary disorders	3/181	4/174
PneumoniaInfections and infestations	0/181	4/174
Acute graft versus host disease in skinImmune system disorders	4/181	1/174

Most frequent other events

Showing 10 of 82

Most frequent other events
Event	Defibrotide Prophylaxis	Best Supportive Care
StomatitisGastrointestinal disorders	105/181	114/174
PyrexiaGeneral disorders	113/181	113/174
DiarrhoeaGastrointestinal disorders	110/181	108/174
NauseaGastrointestinal disorders	109/181	101/174
VomitingGastrointestinal disorders	106/181	91/174
HypokalaemiaMetabolism and nutrition disorders	75/181	63/174
HypertensionVascular disorders	71/181	55/174
HypomagnesaemiaMetabolism and nutrition disorders	71/181	59/174
Febrile neutropeniaBlood and lymphatic system disorders	52/181	59/174
Abdominal painGastrointestinal disorders	57/181	48/174

Baseline characteristics

Baseline characteristics were assessed using the Intent-to-Treat Analysis Set.

Age, Continuous
Age, Continuous(years)	Defibrotide Prophylaxis	Best Supportive Care	Total
Mean	22.7 ± 21.87	23.2 ± 21.73	23.0 ± 21.77

Age, Customized
Age, Customized(Participants)	Defibrotide Prophylaxis	Best Supportive Care	Total
Participants ≤16 Years	104	94	198
Participants >16 Years	86	88	174

Sex: Female, Male
Sex: Female, Male(Participants)	Defibrotide Prophylaxis	Best Supportive Care	Total
Female	90	82	172
Male	100	100	200

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Defibrotide Prophylaxis	Best Supportive Care	Total
Hispanic or Latino	22	21	43
Not Hispanic or Latino	150	143	293
Unknown or Not Reported	18	18	36

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Defibrotide Prophylaxis	Best Supportive Care	Total
American Indian or Alaska Native	0	0	0
Asian	39	46	85
Native Hawaiian or Other Pacific Islander	0	2	2
Black or African American	5	8	13
White	125	109	234
More than one race	2	0	2
Unknown or Not Reported	19	17	36

Study locations

114 sites

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

Showing the first 100 of 114 sites across 14 countries.

References and documents

Study documents

Study protocol · Aug 20, 2018
Statistical analysis plan · Nov 24, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 2, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02851407
Lead sponsor: Jazz Pharmaceuticals
Responsible party: Sponsor
First posted: Aug 1, 2016
Start date: Sep 1, 2016
Primary completion: Oct 20, 2020
Completion: Oct 20, 2020
Results posted: Mar 2, 2022
Last update: Mar 2, 2022

Study contacts

Jazz Pharmaceuticals

study director · Jazz Pharmaceuticals

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2022. You cannot join it, but the record below documents what was studied.

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