PURPOSE: While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined. PATIENTS AND METHODS: The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens. RESULTS: The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m(2) while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2). Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean +/- SE) was 45% +/- 15% and the 1 year event-free survival and overall survival estimates were 38% +/- 14% and 53% +/- 15%, respectively. CONCLUSION: This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.