On September 27, 2006, the U. S. Food and Drug Administration granted accelerated approval to imatinib mesylate (Gleevec, Novartis Pharmaceuticals) as a single agent for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML).
Approval is based upon the induction of both hematologic and cytogenetic responses. A total of 51 pediatric patients with newly diagnosed and untreated chronic phase CML were enrolled in an open-label, multi-center, single arm phase 2 trial. Patients were treated with Gleevec 340 mg/m2/day. Complete hematologic response (CHR) was observed in 78% of evaluable pediatric patients after 8 weeks of therapy. The complete cytogenetic response rate (CCyR) was 65%, comparable to the results observed in adult CML patients. The partial cytogenetic response (PCyR) rate was 16%. The majority of evaluable patients who achieved a CCyR developed the CCyR between months 3 and 10 (median time to response 6.74 months). Estimated 12 month survival was 98% and estimated 24 month survival was 84%.
Imatinib generally was well tolerated. Grade 3 or 4 toxicities were primarily hematologic. Non-hematological grade 3 or 4 toxicities included allergic reaction/hyper-sensitivity, avascular osteonecrosis, and desquamating rash. No deaths occurred on study therapy. Only one patient discontinued study drug due to suspected study drug-related AEs (elevated AST/ALT). Muscle cramps were reported sporadically during the study and there were no episodes of GI hemorrhage. No new safety concerns were raised.
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