Phase 3
N=372
Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients
Veno-occlusive Disease
Bottom Line
View on ClinicalTrials.gov: NCT02851407 ↗Enrolled (actual)
372
Serious AEs
43.9%
Results posted
Mar 2022
Primary outcome: Primary: Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC) — 66.8; 72.5 KM Estimate % of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Defibrotide (Drug); Best Supportive Care (Other)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Jazz Pharmaceuticals
- Primary completion
- Oct 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC) |
66.8; 72.5 | — |
| SECONDARY Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC) |
49.8; 57.1 | — |
| SECONDARY Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) |
47; 38 | — |
| SECONDARY Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
34.6; 42.8 | — |
| SECONDARY Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
80.4; 89.7; 77.9; 81.9 | — |
| SECONDARY 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 |
8; 8; 9; 10 | — |
| SECONDARY Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
6; 15 | — |
| SECONDARY Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
NA; 30.0 | — |
| SECONDARY 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 |
6; 5; 6; 5 | — |
| SECONDARY 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 |
4; 7; 28; 28; 9; 6 | — |
| SECONDARY 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 |
3; 6; 35; 32; 3; 4 | — |
| SECONDARY 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 |
7; 10; 24; 22; 9; 10 | — |
| SECONDARY 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 |
10; 11; 25; 19; 6; 12 | — |
| SECONDARY 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 |
11; 11; 22; 27; 7; 4 | — |
| SECONDARY 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 |
2; 1; 8; 8; 3; 4 | — |
| SECONDARY 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 |
3; 2; 7; 10; 3; 1 | — |
| SECONDARY 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 |
2; 1; 7; 11; 4; 1 | — |
| SECONDARY 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 |
4; 3; 7; 9; 2; 1 | — |
| SECONDARY 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 |
3; 2; 8; 10; 2; 1 | — |
| SECONDARY 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 |
1; 2; 9; 10; 3; 4 | — |
| SECONDARY 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 |
3; 4; 8; 10; 2; 2 | — |
| SECONDARY 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 |
1; 3; 7; 10; 5; 3 | — |
| SECONDARY 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 |
0; 5; 12; 8; 1; 3 | — |
| SECONDARY 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 |
6; 6; 5; 8; 2; 2 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase |
30.4; 40 | — |
| SECONDARY Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase |
61.6; 78.2 | — |
| SECONDARY Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase |
4.7 | — |
| SECONDARY Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase |
7.9; 5.9 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase |
44.4; 39.7 | — |
| SECONDARY Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase |
119.1; 90.7 | — |
| SECONDARY Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase |
6.3; 6.7 | — |
| SECONDARY 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 |
13; 13; 20; 24; 22; 26 | — |
| SECONDARY 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 |
5; 1; 6; 1; 6; 1 | — |
| SECONDARY Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
14; 12; 2; 1 | — |
| SECONDARY Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase |
4; 5; 4; 4 | — |
| SECONDARY Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
156; 162 | — |
| SECONDARY Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) |
154; 163 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Patient must be above the age of 1 month as of the start date of study treatment.
- Patient must be scheduled to undergo allogeneic hematopoietic stem cell transplant (HSCT) (adults or pediatric patients) or autologous HSCT (pediatric patients only) and be at high risk or very high risk of developing veno-occlusive disease (VOD).
- Female patients (and female partners of male patients) of childbearing potential who are sexually active must agree to use a highly effective method of contraception with their partners during exposure to defibrotide and for 1 week after the last dose of defibrotide.
- Adult patients must be able to understand and sign a written informed consent. For minor patients, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT02851407). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.