Phase I Trial and Pharmacokinetic Study of BMS-247550 (NSC 710428, Ixabepilone), an Epothilone B Analog, in Pediatric Patients With Refractory Solid Tumors and Leukemias

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of ixabepilone in young patients with refractory solid tumors (closed to accrual as of 10/4/2007) or relapsed or refractory leukemia.
• Determine the toxicity spectrum of this drug in these patients.
• Determine the plasma pharmacokinetics of this drug in these patients.
• Determine the pharmacodynamics of this drug in these patients.
• Assess the nerve growth factor levels, before and after the initiation of this drug, as a potential surrogate marker for the development of peripheral neuropathy in these patients.

Secondary

• Determine the response of patients treated with this drug.
• Compare the tolerability, toxicity profile, MTD, DLT, pharmacokinetics, and pharmacodynamics of this drug in young patients treated on this study vs adults with solid tumors (closed to accrual as of 10/4/2007) treated on the ongoing Medicine Branch, NCI, phase I study.
• Assess the safety and tolerability of ixabepilone at the solid tumor MTD (expanded leukemia cohort).
• Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed leukemia.
• Evaluate the extent of tubulin polymerization in leukemic blasts at baseline after treatment with ixabepilone ex-vivo.
• Compare the effects of tubulin polymerization in leukemic blasts with ixabepilone versus paclitaxel ex-vivo with an without the presence of a potent P-glycoprotein inhibitor.
• Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic blasts.