EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)

An experimental drug called EZN-3042 targets survivin, a protein expressed in leukemia cells at relapse that promotes the leukemia cells to grow. The main goal of this phase I study is to find out the dose of EZN-3042 that can be safely given without serious side effects both alone and in combination with standard chemotherapy drugs during re-induction.

This is a phase I multi-site study of the new investigational agent EZN-3042, which is highly effective at blocking survivin and inhibiting survivin protein expression. Survivin plays pivotal roles in tumor formation by inhibiting cell death and regulating cell cycle progression. The primary objective is to study EZN-3042 in children with relapsed acute lymphoblastic leukemia (ALL). Patients will receive 2 doses of EZN-3042 (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase. Patients with CNS 1 or 2 will also receive intrathecal methotrexate, and patients with CNS 3 will also receive triple intrathecal therapy (methotrexate, hydrocortisone, and cytarabine). Blood and bone marrow specimens will be drawn to measure minimal residual disease (MRD), pharmacokinetic levels of EZN-3042 and survivin expression. The study will follow a standard 3+3 dose escalation design. We hypothesize that EZN-3042 will be safe, tolerable and biologically active, when given both alone and in combination with standard re-induction chemotherapy.