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

Inclusion Criteria: * Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with acute lymphoblastic leukemia (ALL). * Patients must have relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. * Patients may have central nervous system 1, 2 or 3 disease. * Karnofsky Performance Level ≥ 50 for patients \> 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. * Patients must have had 2 or more prior therapeutic attempts defined as: * Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th…relapse), or * Refractory disease after first or greater relapse and a single re-induction attempt. \*Please note, Enrollment will be restricted to at most one refractory patient in each cohort of 3 patients per dose level. * Patients with ALL who are refractory to frontline induction therapy are not eligible. * Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study. * Patients who relapse when they are not receiving standard ALL maintenance therapy must have fully recovered from grade 3 or 4 toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. * Cytotoxic Therapy: It must be at least 14 days since the completion of cytotoxic therapy (excluding hydroxyurea) at the time of study enrollment. * Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of active Graft-versus-Host Disease (GVHD) and are at least 120 days post-transplant at the time of enrollment. * Prior anthracycline exposure: Patients must have ≤ 400 mg/m2 lifetime exposure of anthracycline chemotherapy. * Biologic (anti-neoplastic) therapy: It must be at least 7 days since the completion of therapy with a biologic agent at the time of study enrollment. For agents that have known adverse events occurring 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Patients must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2 OR a normal serum creatinine based on the institutional normal values according to age. * Patient's ALT must be \< 5 x institutional upper limit of norm (ULN), unless the elevation is suspected to be disease-related. * Patient's total bilirubin must be ≤ 1.5 x ULN. * Patient's serum albumin must be ≥ 2 g/dL. * Patient must have prothrombin time (PT), partial thromboplastin time (PTT) and international normalized ratio (INR) ≤ 1.5 times the ULN. * Patient must have a shortening fraction ≥ 27% by echocardiogram or an ejection fraction ≥ 45% by gated nucleotide study. * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. Exclusion Criteria: * Patients with Down syndrome are excluded. * Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible * Patients who cannot receive asparaginase on this study due to prior pancreatitis, stroke or other toxicity are not eligible. * Patients with clinically significant prior allergies to PEG asparaginase are eligible if Erwinia L-asparaginase can be substituted. The study will not supply Erwinia. * Patients who initially receive asparaginase, but must discontinue due to toxicity, remain eligible. * Patients with documented active and uncontrolled infection at the time of study entry are not eligible. * Patient will be excluded if they are currently receiving other investigational drugs. * Patients will be excluded if they are taking strong CYP3A4 inducers or inhibitors. * Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period. * Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.