Prevention of Hepatic Veno-Occlusive Disease following Hematopoietic Stem Cell Transplant MedDRA version: 19.0 Level: LLT Classification code 10047207 Term: Veno-occlusive liver damage System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 19.0 Level: LLT Classification code 10047217 Term: Venoocclusive syndrome of the liver System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 19.0 Level: PT Classification code 10047216 Term: Venoocclusive liver disease Syste
Conditions
Sponsors
Jazz Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be above the age of 1 month as of the start date of study treatment. 2. Patient must be scheduled to undergo allogeneic (adults or pediatric patients) or autologous HSCT (pediatric patients only) and be at high risk or very high risk of developing VOD. a. High-risk patients must meet both of the following criteria (i and ii): i. Patient must be scheduled to receive myeloablative conditioning, defined as either of the following: a. At least 2 alkylating agents (e.g., cyclophosphamide, busulfan, melphalan); the investigator must document in the medical chart that the conditioning regimen is considered to be myeloablative or b. TBI (single dose of =5 Gy, or =8 Gy fractionated dose) and at least 1 alkylating agent, and ii. Patient must meet at least 1 of the following criteria (a or b): a. Have at least 1 hepatic-related risk factor, as defined by the EBMT position statement at screening: • Transaminase level >2.5 times the upper limit of normal (ULN) • Serum total bilirubin level >1.5 times the ULN • Cirrhosis (with biopsy evidence) • Hepatic fibrosis (by histology) • Known history of active viral hepatitis within 1 year before the start of study treatment, as indicated by an available positive test result for any of the following: hepatitis A virus (HAV) immunoglobulin M (IgM) antibody; hepatitis B virus (HBV) core IgM antibody; HBV surface antigen; hepatitis C virus (HCV) antibody with HCV polymerase chain reaction (PCR) test (or HCV PCR alone) • Any prior hepatic irradiation, including abdominal irradiation covering the hepatic area • Documented diagnosis of iron overload (serum ferritin >2000 ng/mL) or b. Has advanced-stage neuroblastoma requiring myeloablative conditioning b. Very high-risk patients must meet one of the following criteria: i. Osteopetrosis and undergoing myeloablative conditioning ii. Primary HLH, Griscelli II Chediak-Higashi syndrome, Hermansky-Pudiak II, X-linked lymphoproliferative disorders, X-linked severe combined immunodeficiency, X-linked hypogammaglobulinemia, or familial HLH 1-5 and undergoing myeloablative conditioning iii.Prior treatment with an ozogamicin-containing monoclonal antibody using the minimum dose and schedule, according to the patient prescribong information; iv.Class III, high-risk thalassemia (i.e., patients who are =7 years old and have a liver size =5 cm at the time of screening 3. Female patients of childbearing potential who are sexually active must agree to use a medically acceptable method of contraception throughout the entire study period and for 4 weeks after the last dose of study drug; male patients with female partners of childbearing potential must agree to use a medically acceptable method of contraception for 6 months after the last dose of study drug. Medically acceptable methods of contraception that may be used by the patient and/or partner include abstinence, birth control pills, patches, vaginal ring, diaphragm and spermicide, condom and vaginal spermicide, surgical sterilization, vasectomy (>6 months before Study Day 1), and progestin implant or injection. Post-menopausal women (i.e., women with >2 years of amenorrhea) do not need to use contraception. 4. Patient and/or the legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate. Are the trial subjects under 18? yes Number of subjects for this age range: 195 F.1.2 Adults (
Exclusion criteria
Exclusion criteria: 1. Patient has hemodynamic instability within 24 hours before the start of study treatment. 2. Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment, defined as either of the following: a. hemorrhage requiring >15 cc/kg of packed red blood cells (e.g., pediatric patient weighing 20 kg and requiring 300 cc packed red blood cells/24 hours, or an adult weighing >70 kg and requiring 3 units of packed red blood cells/24 hours) to replace blood loss, or b. bleeding from a site which, in the investigator’s opinion, constitutes a potential life-threatening source (e.g., pulmonary hemorrhage or central nervous system bleeding), irrespective of amount of blood loss 3. Patient used any medication that increases the risk of bleeding within 24 hours before the start of study treatment, including, but not limited to, systemic heparin, low molecular weight heparin, heparin analogs, alteplase, streptokinase, urokinase, ATIII, and oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Note: Heparin used to keep catheters open will be allowed (up to a maximum of 100 U/kg/day). 4. Patient is using or plans to use an investigational agent for the prevention or treatment of VOD. 5. Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. 6. Patient has a psychiatric illness that would prevent the patient or legal guardian or representative from giving informed consent and/or assent. 7. Patient has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study. 8. Patient is pregnant or lactating and does not agree to stop breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the efficacy of defibrotide vs Best Supportive Care for the prevention of Veno-Occlusive Disease (VOD) as measured by VOD-free survival by Day +30 post-HSCT in patients who are at high risk or very high risk for developing VOD.;Secondary Objective: The key secondary objective of the study is to compare the efficacy of defibrotide vs BSC for the prevention of VOD as measured by VOD-free survival by Day +100 post-HSCT in patients who are at high risk or very high risk for developing VOD;Primary end point(s): The primary efficacy endpoint is the VOD-free survival rate by Day +30 post-HSCT, as adjudicated by the independent Endpoint Adjudication Committee (EPAC).;Timepoint(s) of evaluation of this end point: Day +30 post- HSCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is VOD-free survival by Day +100 post-HSCT;Timepoint(s) of evaluation of this end point: Day +100 post-HSCT | — |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, New Zealand, Singapore, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Jazz Pharmaceuticals, Inc.
Outcome results
None listed