Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

PRIMARY OBJECTIVES: I. To determine the toxicities and tolerability of bortezomib in combination with standard-relapse AML therapy (idarubicin/cytarabine or etoposide/high-dose cytarabine) in pediatric and young adult patients with relapsed or primary-refractory or secondary AML. II. To estimate the complete response rate to the Arm A and Arm B regimens. SECONDARY OBJECTIVES: I. To determine whether bortezomib inhibits proteasome activity, NF-kB activity and induces apoptosis pathway proteins in leukemia myeloblasts. II. To determine the feasibility of measuring AML stem cells in relapsed and recovering bone marrow. OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are stratified according to anthracycline\*-equivalent cumulative exposure (≤ 400 mg/m² vs \> 400 mg/m²). Patients are assigned to 1 of 2 groups. GROUP I (efficacy phase, patients with ≤ 400 mg/m² anthracycline-equivalent cumulative exposure - Closed as of 08/01/10): Patients receive idarubicin IV over 15 minutes on days 1-3, low-dose cytarabine IV continuously over days 1-7, and bortezomib IV on days 1, 4, and 8. GROUP II (dose-finding phase (closed as of 10/10) and efficacy phase, patients with \> 400 mg/m² anthracycline\*-equivalent cumulative exposure): Patients receive etoposide IV over 1 hour on days 1-5, high-dose cytarabine IV over 1 hour twice daily on days 1-5, and bortezomib IV on days 1, 4, and 8. NOTE: \* Anthracycline restriction no longer required for group 2 as of 10/02/10. All patients receive intrathecal cytarabine prior to courses 1 and 2. In both arms, treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for at least 5 years.