Treatment of Children with Relapsed Acute Myeloid Leukemia with Gemtuzumab in Combination with Mitoxantrone and Cytarabine.

Despite improvements in the treatment of children with de novo acute myeloid leukemia (AML), a substantial fraction of patients experience relapse. The Children’s Oncology Group Phase I trial, AAML00P2, sought to test the safety and feasibility of combining Gemtuzumab (GMTZ) with a standard AML reinduction regimen of mitoxantrone and cytarabine in a dose de-escalation design. Patients received cytarabine 1000 mg/m2/dose every 12 hours on days 1–4 with mitoxantrone 12 mg/m2/dose daily on days 3–6. The starting dose of GMTZ for dose finding was 3 mg/m2 once on day 7. Doses for patients under 3 years of age were as follows: cytarabine 33 mg/kg/dose, mitoxantrone 0.4 mg/kg/dose, and GMTZ 0.1 mg/kg/dose. Three patients were enrolled in the dose finding strata and an additional 18 patients were subsequently enrolled to acquire further toxicity data. Of these, 15 were male and 6 female. The median patient age was 11.3 years, range 1.2 to 19.2 years. No patients in the initial dose finding cohort experienced a dose limiting toxicity. Toxicities observed in the entire cohort of 21 patients included hematologic and infectious complications typical of AML therapy. One patient had grade III bilirubin elevation. No patients had grade III or IV hepatic toxicity or grade III or IV veno-occlusive disease (VOD). Data on toxicity in stem cell transplant post GMTZ exposure is limited. However, no episodes of VOD have been reported. In summary, GMTZ combined with cytarabine and mitoxantrone is reasonably well tolerated in pediatric AML patients.