14 CLINICAL STUDIES

The efficacy of IDAMYCIN PFS was evaluated in four randomized, controlled clinical studies (Memorial Sloan Kettering Cancer Center (MSKCC), Southeastern Cancer Study Group (SEG), US Multicenter, and Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) trials) of 823 adult patients with newly-diagnosed AML. Patients were randomized to receive either idarubicin hydrochloride (IDR) or daunorubicin (DNR) in combination with cytarabine (Ara C) as induction therapy. Median age for IDR versus DNR in the MSKCC, SEG, US Multicenter, and GIMEMA studies was 36 versus 41, 60 versus 61, 56 versus 55, and 63 versus 62 years, respectively. Incidence of male sex was 45% versus 46%, 53% versus 47%, 57% versus 56%, and 52% versus 59%, respectively.

Idarubicin hydrochloride was administered as an induction regimen of 12 mg/m2 (or 13 mg/m2 [1.1 times the recommended dosage] in US Multicenter study only) once a day for 3 days in combination with cytarabine. Daunorubicin was administered as an induction regimen of 45 mg/m2 (or 50 mg/m2 in MSKCC study only) daily for 2 days. Cytarabine was administered 100 mg/m2 daily by continuous infusion for 7 days or as 25 mg/m2 intravenous bolus followed by 200 mg/m2 daily for 5 days continuous infusion (MSKCC only). Patients who had persistent leukemia after the first induction course could receive a second course of induction therapy.

Patients received the same anthracycline for consolidation as was used for induction, in combination with cytarabine (and 6-thioguanine for the SEG study only). The SEG study also included maintenance therapy with the same anthracycline used in induction in combination with cytarabine. The efficacy or safety have not been established for IDAMYCIN PFS for use as consolidation or maintenance therapy. Efficacy results for the four trials are provided in Table 4.