DEFIBROTIDE FOR PATIENTS WITH HEPATIC VENO-OCCLUSIVE DISEASE (VOD): A TREATMENT IND STUDY (UNDER CFR 312.34)
The primary purpose of this protocol is to provide defibrotide to patients with severe VOD. Because this drug has not been approved by the FDA, use of this medication under the auspices of this IND treatment plan is for compassionate use only.
Clinical diagnosis of VOD, defined by jaundice (bilirubin â?¥2 mg/dL)and at least 2 of the following clinical findings, by Day +21 post stem cell transplant: -ascites, -weight gain greater than 5% above baseline weight (defined as weight on the first day of conditioning-- if this value is not available, the weight on the date of admission to the SCT unit may be used), -hepatomegaly; patients with pre-existing hepatomegaly must have documentation by physical exam or imaging that liver size is increased over baseline (at the time of admission for SCT). Severe VOD, defined as VOD with multi-organ failure (MOF), i.e., presence of one or both of the following, by Day +28 post stem cell transplant: -renal dysfunction: a) serum creatinine greater than 3x value on the date of admission to the SCT unit for conditioning or greater than 3x lowest value during conditioning prior to SCT (whichever is lowest) or b) creatinine clearance or GFR less than 40% of admission value, or c) dialysis dependence; - pulmonary dysfunction: documentation of oxygen saturation less than 90% on room air (two consecutive measurements at least one hour apart) or requirement for oxygen supplementation /ventilator dependence. Dysfunction must be attributable to fluid overload or mechanical impingement from abdominal distention or hepatic enlargement and not to an infectious cause (e.g., documented pneumonia).
The daily dose of Defibrotide (6.25 mg/kg Q6H) will be based on the patientâ??s baseline weight, defined as weight on the first day of conditioning. (If this value is unavailable, the weight on the date of admission to the SCT unit may be used). Each of the 4 divided doses per day will be rounded to the nearest 10 mg for adults ( greater than 35 kg) and the nearest 5 mg for children ( less than 35 kg) in order to facilitate efficient drug administration. Total daily dose for all patients will be 25 mg/kg.
09/18/2014 04:03 AM