A Phase 3, Randomized, Adaptive Study Comparing the Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant

Jazz Pharmaceuticals, Inc.0 个研究点目标入组 400 人开始时间: 2016年8月18日最近更新: 2020年12月14日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Jazz Pharmaceuticals, Inc.
入组人数: 400

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

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研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•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
•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. Has at least 1 hepatic-related risk factor, as defined by the European Society for Blood and Marrow Transplantation (EBMT) position statement, during screening as follows:
•Transaminase level >2.5 times the upper limit of normal (ULN) during screening or within 14 days prior to screening on a non-screening test if the test was performed as part of patient’s routine standard of care
•Serum total bilirubin level >1.5 times the ULN during screening or within 14 days prior to screening on a non-screening test if the test was performed as part of patient’s routine standard of care
•Prior history of cirrhosis (with biopsy evidence)
•Prior history of hepatic fibrosis (by histology or other diagnostic scoring system per institutional guidelines)
•Prior history of viral hepatitis within 1 year before the start of study treatment as indicated by a positive test for any of the following:
•– hepatitis A virus (HAV) immunoglobulin M (IgM) (anti-HAV IgM)
•– hepatitis B virus (HBV) core immunoglobulin G (IgG) or IgM (anti-HBc IgG or anti-HBc IgM)
•– HBV surface antigen (HBsAg)
•– HBV DNA by polymerase chain reaction (PCR) or nucleic acid amplification testing (NAAT)
•– hepatitis C virus (HCV) antibody (anti-HCV) and HCV RNA by PCR or NAAT
•Any prior hepatic irradiation, including abdominal irradiation covering the hepatic area
•Documented diagnosis of iron overload or liver iron content =5.0 mg/gdw as estimated by magnetic resonance imaging T2* within 3 months prior to screening.
•b. Has advanced-stage neuroblastoma requiring myeloablative conditioning.
•b. Very high-risk patients must meet 1 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 prescribing information;
•examples include the following:
•Gemtuzumab ozogamicin, at least 9 mg/m2 total dose
•Inotuzumab ozogamicin, at least 1.5 mg/mg2 over 28 days
•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 (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. Highly e

排除标准

•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 or b):
•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 (tPA), streptokinase, urokinase,
•antithrombin III (ATIII), and oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Patients may receive heparin or other anticoagulants for routine central venous line management and intermittent dialysis or ultrafiltration. Fibrinolytic instillation for central venous line occlusion is also permitted. Note: Heparin use will be allowed in both treatment arms (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 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.
•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.
•9. Patient has a known history of hypersensitivity to defibrotide or any of the excipients.
•10. Patient or parent/legal guardian or representative lacks the full mental capacity to understand and sign a written informed consent.
•11. Patient is receiving or plans to receive other investigational therapy during study.

研究者

发起方

Jazz Pharmaceuticals, Inc.

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