increased, Lipase increased, Pancreatic necrosis, Pancreatitis, Pancreatitis relapsing;
Abnormal clotting studies: Activated partial thromboplastin time prolonged, Blood fibrinogen decreased; Diarrhea:
Colitis, Diarrhea, Enterocolitis, Neutropenic colitis; Hypersensitivity: Anaphylactic reaction, Drug hypersensitivity,Hypersensitivity; Embolic and thrombotic events SMQ: Device related thrombosis, Disseminated intravascularcoagulation, Embolism, Intracardiac thrombus, Intracranial venous sinus thrombosis, Pulmonary embolism, Superiorsagittal sinus thrombosis, Thrombosis in device, Venous thrombosis, Venous thrombosis limb; Sepsis:
Bacterialsepsis, Sepsis; Dyspnea: Hypoxia, Respiratory failure; Hemorrhages SMQ (excludes laboratory terms):
Disseminated intravascular coagulation, Epistaxis, Hematoma, Hemorrhage intracranial, Melena, Esophageal ulcerhemorrhage, Small intestinal hemorrhage, Upper gastrointestinal hemorrhage; Fungal infection: Fungal infection,Hepatic infection fungal, Respiratory tract infection fungal, Splenic infection fungal, Systemic candida; Pneumonia:
Lung infection, Pneumonia, Pneumonitis; Arrhythmia: Atrioventricular block complete, Sinus tachycardia, Ventriculararrhythmia; Cardiac failure: Ejection fraction decreased, Left ventricular dysfunction.
§ Grading is based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
In the subgroup of patients with B-cell lineage ALL, the complete remission rate in the ASPARLASarm was 98% (95/97), compared to 99% in the pegaspargase arm; the Kaplan-Meier estimates of overallsurvival of the treatment arms were comparable.
Study AALL07P4
The safety of ASPARLAS was also eva luated in Study AALL07P4, an open-label, randomized,active-controlled, multicenter clinical trial that treated patients with newly-diagnosed high-risk B-precursorALL using ASPARLAS 2,500 U/m2 (n=43) or 2,100 U/m2 (n=68), or pegaspargase 2,500 U/m2 (n=52), as a component of an augmented Berlin-Frankfurt-Münster (BFM) therapy regimen. The median age was
11 years (range 1 to 26 years); the median duration of exposure was 7 months for both ASPARLAS andpegaspargase. In this study, the induction mortality of patients treated with ASPARLAS was 2.8% (3 outof 111); there were no induction deaths among 52 patients treated with pegaspargase.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on the use of ASPARLAS in pregnant women to inform a drug-associatedrisk of major birth defects and miscarriage. Published literature studies in pregnant animals suggestasparagine depletion may cause harm to the animal offspring (see Data). Advise patients of the potentialrisk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. generalpopulation, the estimated background risk of major birth defects and miscarriage in clinically recognizedpregnancies are 2%-4% and 15%-20%, respectively.
Data
Animal Data
Animal reproduction studies have not been conducted with ASPARLAS to eva luate its effect onreproduction and fetal development. Published literature studies in which pregnant rabbits wereadminist |
