Trial Outcomes & Findings for Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients (NCT NCT02851407)

Last Updated: 2022-03-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

372 participants

Primary outcome timeframe

Day +30 Post-HSCT

Results posted on

2022-03-02

Participant Flow

Participants, their parents/legal guardians, or representatives were required to sign a statement of informed consent.

Participant milestones

Participant milestones
Measure	Defibrotide Prophylaxis Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Study STARTED	190	182
Overall Study COMPLETED	120	121
Overall Study NOT COMPLETED	70	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Defibrotide Prophylaxis Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Study Withdrawal by parent/guardian	2	7
Overall Study Protocol deviation	0	1
Overall Study Transferred to another hospital to continue	1	0
Overall Study Other Death	30	20
Overall Study Adverse event, serious fatal	6	8
Overall Study Consent withdrawn by participant	5	3
Overall Study Screen failure	2	1
Overall Study Disease relapse	9	6
Overall Study Physician Decision	7	6
Overall Study Transferred to hospital closer to home	0	1
Overall Study Enrolled in an investigational study	0	1
Overall Study Early recovery	1	0
Overall Study Adverse event, non-fatal	7	5
Overall Study Lost to Follow-up	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable. Best Supportive Care	Total n=372 Participants Total of all reporting groups
Age, Continuous	22.7 years STANDARD_DEVIATION 21.87 • n=5 Participants	23.2 years STANDARD_DEVIATION 21.73 • n=7 Participants	23.0 years STANDARD_DEVIATION 21.77 • n=5 Participants
Age, Customized Participants ≤16 Years	104 Participants n=5 Participants	94 Participants n=7 Participants	198 Participants n=5 Participants
Age, Customized Participants >16 Years	86 Participants n=5 Participants	88 Participants n=7 Participants	174 Participants n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	82 Participants n=7 Participants	172 Participants n=5 Participants
Sex: Female, Male Male	100 Participants n=5 Participants	100 Participants n=7 Participants	200 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	21 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	150 Participants n=5 Participants	143 Participants n=7 Participants	293 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	46 Participants n=7 Participants	85 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	125 Participants n=5 Participants	109 Participants n=7 Participants	234 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day +30 Post-HSCT

Population: VOD-free survival was assessed using the Intent-to-Treat Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)	66.8 KM Estimate % of participants Interval 57.8 to 74.4	72.5 KM Estimate % of participants Interval 62.3 to 80.4

SECONDARY outcome

Timeframe: Day +100 Post-HSCT

Population: VOD-free survival was assessed using the Intent-to-Treat Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)	49.8 KM Estimate % of participants Interval 26.1 to 69.5	57.1 KM Estimate % of participants Interval 36.6 to 73.1

SECONDARY outcome

Timeframe: Day +30 Post-HSCT

Population: Percentage of Participants with VOD by Day +30 post-HSCT was assessed using the Intent-to-Treat Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)	47 Participants	38 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: VOD-free Survival by Day +180 post-HSCT was assessed using the Intent-to-Treat Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	34.6 KM Estimate % of participants Interval 18.2 to 51.8	42.8 KM Estimate % of participants Interval 26.7 to 58.0

SECONDARY outcome

Timeframe: Days +100 and +180 Post-HSCT

Population: Non-relapse mortality was assessed using the number of participants with malignant primary disease within treatment arm from the Intent-to-Treat Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=147 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=139 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +100 Post-HSCT	80.4 KM Estimate % of non-relapse survival Interval 71.6 to 86.8	89.7 KM Estimate % of non-relapse survival Interval 82.1 to 94.2
Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-HSCT	77.9 KM Estimate % of non-relapse survival Interval 68.4 to 84.9	81.9 KM Estimate % of non-relapse survival Interval 70.8 to 89.1

SECONDARY outcome

Timeframe: Days +30 and +100 Post-HSCT

Population: Percentage of Participants with VOD-associated MOD was assessed using the Intent-to-Treat Analysis Set.

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."

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Day +30 Post-HSCT	8 Participants	8 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 Day +100 Post-HSCT	9 Participants	10 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Resolution of VOD was assessed using the Intent-To-Treat Analysis Set. The overall number analyzed is the number of participants diagnosed with VOD by Day +30 post-HSCT by the investigator.

The proportion of participants who had resolution of VOD by Day +180 post-HSCT is reported as a percentage.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=23 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=29 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	6 Participants	15 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Resolution of VOD was assessed using the Intent-To-Treat Analysis.

Time to Resolution of VOD is calculated as follows: Time to Resolution of VOD= \[Date of VOD resolution\] - \[Date of VOD diagnosis by investigator\].

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	NA Days Not assessable. There were not enough participants who had VOD resolution for this to be estimated. The value is not estimable because the number of VOD resolution, i.e 6, is less than half of the number of diagnosed VOD in the DP arm, so the KM estimate of median time cannot be evaluated.	30.0 Days Interval 21.0 to 48.0

SECONDARY outcome

Timeframe: Days +100 and +180 Post-HSCT

Population: Percentage of VOD was assessed using the Intent-to-Treat Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=190 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=182 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Day +100 Post-HSCT	6 Participants	5 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 Day +180 Post-HSCT	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-5L Mobility was assessed using the Age ≥ 16 Years Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=45 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=46 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	4 Participants	7 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 Condition unchaged	28 Participants	28 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 Condition deteriorated	9 Participants	6 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 Unknown	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-5L Self-Care was assessed using the Age ≥ 16 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=45 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=46 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	3 Participants	6 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 Condition unchaged	35 Participants	32 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 Condition deteriorated	3 Participants	4 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 Unknown	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-5L Activity was assessed using the Age ≥ 16 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=45 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=46 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition deteriorated	9 Participants	10 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 Condition improved	7 Participants	10 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 Condition unchaged	24 Participants	22 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 Unknown	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-5L Pain was assessed using the Age ≥ 16 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=45 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=46 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Unknown	4 Participants	4 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 Condition improved	10 Participants	11 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 Condition unchaged	25 Participants	19 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 Condition deteriorated	6 Participants	12 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-5L Anxiety was assessed using the Age ≥ 16 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=45 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=46 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	11 Participants	11 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 Condition unchaged	22 Participants	27 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 Condition deteriorated	7 Participants	4 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 Unknown	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Mobility was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=15 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=15 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	2 Participants	1 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 Condition unchanged	8 Participants	8 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 Condition deteriorated	3 Participants	4 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 Unknown	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Self-Care was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=15 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=15 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition unchanged	7 Participants	10 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 Condition deteriorated	3 Participants	1 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 Unknown	2 Participants	2 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 Condition improved	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Activity was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=15 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=15 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	2 Participants	1 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 Condition unchanged	7 Participants	11 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 Condition deteriorated	4 Participants	1 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 Unknown	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Pain was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=15 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=15 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Unknown	2 Participants	2 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 Condition improved	4 Participants	3 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 Condition unchanged	7 Participants	9 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 Condition deteriorated	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Anxiety was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=15 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=15 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	3 Participants	2 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 Condition unchanged	8 Participants	10 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 Condition deteriorated	2 Participants	1 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 Unknown	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Mobility at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=14 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=17 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	1 Participants	2 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 Condition unchanged	9 Participants	10 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 Condition deteriorated	3 Participants	4 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 unknown	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Self-Care at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=14 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=17 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	3 Participants	4 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 Condition unchanged	8 Participants	10 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 Condition deteriorated	2 Participants	2 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 Unknown	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Activity at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=14 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=17 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition improved	1 Participants	3 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 Condition unchanged	7 Participants	10 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 Condition deteriorated	5 Participants	3 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 Unknown	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Pain at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=14 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=17 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Condition unchanged	12 Participants	8 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 Condition improved	0 Participants	5 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 Condition deteriorated	1 Participants	3 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 Unknown	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: EQ-5D-Y Pain at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=14 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=17 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Unknown	1 Participants	1 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 Condition improved	6 Participants	6 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 Condition unchanged	5 Participants	8 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 Condition deteriorated	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day +1 and +7 Post-HSCT

Population: Cmax was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=2 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 Post-HSCT	30.4 μg/mL Standard Deviation 10.600	—
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +7 Post-HSCT	40 μg/mL Standard Deviation 3.168	—

SECONDARY outcome

Timeframe: Day +1 and +7 Post-HSCT

Population: AUClast was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=2 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 Post-HSCT	61.6 h*μg/mL Standard Deviation 28.488	—
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +7 Post-HSCT	78.2 h*μg/mL Standard Deviation 10.781	—

SECONDARY outcome

Timeframe: Day +1 and +7 Post-HSCT

Population: Mean clearance was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=2 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 Post-HSCT	4.7 L/h Standard Deviation 0.304	—

SECONDARY outcome

Timeframe: Day +1 and +7 Post-HSCT

Population: Volume of distribution was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=2 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 Post-HSCT	7.9 L Standard Deviation 0.689	—
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase Day +7 Post-HSCT	5.9 L Standard Deviation 1.609	—

SECONDARY outcome

Timeframe: Day +14 Post-VOD Treatment

Population: Cmax was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=4 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=14 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase	44.4 μg/mL Standard Deviation 18.550	39.7 μg/mL Standard Deviation 25.775

SECONDARY outcome

Timeframe: Day +14 Post-VOD Treatment

Population: AUClast was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=4 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=14 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase	119.1 h*μg/mL Standard Deviation 68.875	90.7 h*μg/mL Standard Deviation 54.798

SECONDARY outcome

Timeframe: Day +14 Post-VOD Treatment

Population: Volume of distribution was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=2 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=9 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase	6.3 L Standard Deviation 0.654	6.7 L Standard Deviation 5.895

SECONDARY outcome

Timeframe: Days +30, +100, and +180 Post-HSCT

Population: Percentage of participants with acute GvHD was assessed using the Safety Analysis Set. Percentages were calculated with the number of participants in Safety Analysis Set who entered the study phase in each arm as a denominator during 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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=147 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=142 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Day +30 Post-HSCT	13 Participants	13 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 Day +100 Post-HSCT	20 Participants	24 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 Day +180 Post-HSCT	22 Participants	26 Participants

SECONDARY outcome

Timeframe: Days +30, +100, and +180 Post-HSCT

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=23 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=28 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
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 Day +180 Post-HSCT	6 Participants	1 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 Day +30 Post-HSCT	5 Participants	1 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 Day +100 Post-HSCT	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Percentage of participants chronic GvHD was assessed using the Safety Analysis Set. Percentages were calculated with the number of participants in Safety Analysis Set who entered the study phase in each arm as a denominator. The number analyzed differs from the overall number of participants analyzed due to the count of participants included in the prophylaxis phase versus the rescue phase.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=181 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=174 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Prophylaxis Phase	14 Participants	12 Participants
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Rescue Phase	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Number of Participants with graft failure was assessed using the Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=181 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=174 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase Prophylaxis Phase	4 Participants	5 Participants
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase Rescue Phase	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Number of participants with neutrophil engraftment was assessed using the Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=181 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=174 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	156 Participants	162 Participants

SECONDARY outcome

Timeframe: Day +180 Post-HSCT

Population: Number of Participants with platelet engraftment was assessed using the Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Defibrotide Prophylaxis n=181 Participants Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.	Best Supportive Care n=174 Participants Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)	154 Participants	163 Participants

Adverse Events

Defibrotide Prophylaxis

Serious events: 82 serious events

Other events: 180 other events

Deaths: 35 deaths

Best Supportive Care

Serious events: 74 serious events

Other events: 174 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 215-870-9177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place