Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients
- Conditions
- Veno-occlusive Disease
- Interventions
- Other: Best Supportive Care
- Registration Number
- NCT02851407
- Lead Sponsor
- Jazz Pharmaceuticals
- Brief Summary
This study is to compare the efficacy and safety of defibrotide prophylaxis in addition to best supportive care versus best supportive care alone in the prevention of hepatic veno- occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem cell transplant who are at high risk or very high risk of developing VOD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 372
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Best Supportive Care 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 Defibrotide 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
- Primary Outcome Measures
Name Time Method Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC) Day +30 Post-HSCT 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.
- Secondary Outcome Measures
Name Time Method Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC) Day +100 Post-HSCT 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.
Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +30 Post-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.
Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-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.
Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Days +100 and +180 Post-HSCT 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.
Percentage of Participants With Veno-Occlusive Disease (VOD)-Associated Multi-Organ Dysfunction (MOD) by Days +30 and Days +100 Post-Hematopoietic Stem Cell Transplant (HSCT) in Patients Who Developed VOD Days +30 and +100 Post-HSCT 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."
Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-HSCT The proportion of participants who had resolution of VOD by Day +180 post-HSCT is reported as a percentage.
Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-HSCT Time to Resolution of VOD is calculated as follows: Time to Resolution of VOD= \[Date of VOD resolution\] - \[Date of VOD diagnosis by investigator\].
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 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
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 Day +180 Post-HSCT 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.
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 and +7 Post-HSCT 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.
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 and +7 Post-HSCT 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.
Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 and +7 Post-HSCT 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.
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase Day +1 and +7 Post-HSCT 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.
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase Day +14 Post-VOD Treatment 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.
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase Day +14 Post-VOD Treatment 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.
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase Day +14 Post-VOD Treatment 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.
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 Days +30, +100, and +180 Post-HSCT 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.
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 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.
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-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.
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase Day +180 Post-HSCT 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.
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-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.
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) Day +180 Post-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.
Trial Locations
- Locations (114)
Osaka City University Hospital
🇯🇵Osaka, Japan
Medical Hospital Tokyo Medical and Dental University
🇯🇵Tokyo, Japan
Severance Hospital at Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Alfred I Dupont Hospital For Children
🇺🇸Wilmington, Delaware, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
UZ Gent
🇧🇪Gent, Belgium
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hôpital Saint Antoine
🇫🇷Paris, France
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Institut Paoli Calmettes
🇫🇷Marseille, France
Universitätsklinikum Münster
🇩🇪Münster, Nordrhein-Westfalen, Germany
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Sachsen, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Schneider Children Medical Center of Israel
🇮🇱Petaẖ Tiqwa, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
11. Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G M Lancisi G Salesi
🇮🇹Ancona, Italy
Azienda Ospedaliero - Universitaria
🇮🇹Catania, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
AORMN Marche Nord
🇮🇹Pesaro, Italy
Anjo Kosei Hospital
🇯🇵Anjo, Japan
Kobe University Hospital
🇯🇵Hyōgo, Japan
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Italy
Hokkaido University Hospital
🇯🇵Sapporo, Japan
Erciyes University Medical Faculty
🇹🇷Kayseri, Talas, Turkey
Medicana International Ankara Hospital
🇹🇷Ankara, Turkey
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Toranomon Hospital
🇯🇵Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Auckland City Hospital
🇳🇿Auckland, New Zealand
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Vall d Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital Sant Joan de Deu - PIN
🇪🇸Esplugues de Llobregat, Spain
Hospital Infantil Universitario Niño Jesus
🇪🇸Madrid, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Rady Childrens Hospital San Diego
🇺🇸San Diego, California, United States
Ann and Robert H Lurie Childrens Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University Hospital Case Medical Center
🇺🇸Cleveland, Ohio, United States
Nicklaus Childrens Hospital
🇺🇸Miami, Florida, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Stanford University
🇺🇸Palo Alto, California, United States
Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Tufts Floating Hospital for Children
🇺🇸Boston, Massachusetts, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Royal Children's Hospital Melbourne
🇦🇺Melbourne, Victoria, Australia
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Sainte Justine Hospital
🇨🇦Montreal, Quebec, Canada
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, United States
Medical University of South Carolina - PPDS
🇺🇸Charleston, South Carolina, United States
Cook Childrens Hospital
🇺🇸Fort Worth, Texas, United States
Texas Childrens Hospital
🇺🇸Houston, Texas, United States
Centre Hospitalier Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
CHU de Poitiers
🇫🇷Poitiers, France
Klinikum Frankfurt Oder GmbH
🇩🇪Frankfurt (Oder), Brandenburg, Germany
Universitätsklinikum der RWTH Aachen
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Rambam Health Corporation
🇮🇱Haifa, Israel
Hadassah Ein Kerem Hospital
🇮🇱Jerusalem, Israel
Hamanomachi Hospital
🇯🇵Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Hyogo College of Medicine
🇯🇵Nishinomiya, Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
🇯🇵Tokyo, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga Hospital General
🇪🇸Malaga, Spain
Akdeniz University Medical Faculty Department of Pediatrics
🇹🇷Antalya, Konyaalti, Turkey
St. James University Hospital
🇬🇧Leeds, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Medical Park Antalya Hospital
🇹🇷Antalya, Turkey
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
Ege Universitesi Tip Fakultesi
🇹🇷Bornova, Turkey
Acibadem Universitesi Tip Fakultesi Atakent Hastanesi
🇹🇷Istanbul, Turkey
Acibadem Adana Hospital
🇹🇷Seyhan, Turkey
Royal Hospital for Children
🇬🇧Glasgow, United Kingdom
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hopital Jean Minjoz
🇫🇷Besançon, France
Colorado Children's Hospital
🇺🇸Aurora, Colorado, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Institut Universitaire du Cancer de Toulouse - Oncopôle
🇫🇷Toulouse, France
Klinikum der Universitat Regensburg
🇩🇪Regensburg, Germany
National Hospital Organization Kumamoto Medical Center
🇯🇵Kumamoto, Japan
Kanagawa Children's Medical Center
🇯🇵Kanagawa, Japan
Japanese Red Cross Nagoya Daiichi Hospital
🇯🇵Nagoya, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan