Safety of Clofarabine With Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia

Inclusion Criteria: * 1 to 21 years old at the date of acute lymphoblastic leukemia initial diagnosis * Very early medullary first relapse occurring during the first 18th months after complete remission OR patients with second relapse OR a relapse occurring 6 months or more after myeloablative stem cell transplantation will be eligible. * Have a Karnofsky Performance Status (KPS) of ≥70 for patients \>10 years of age or a Lansky Performance Status (LPS) of ≥60 for patients ≤10 years of age. * No concomitant malignant disease. * No active uncontrolled infection. * Have adequate renal and hepatic functions * absence of concomitant severe cardiovascular disease, i.e. congestive heart failure * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Exclusion Criteria: * Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. * Use of any investigational agent within 30 days. * Known hypersensitivity to clofarabine or excipients. * Known hypersensitivity to mitoxantrone, etoposide or excipients. * Allergy to both E Coli-Asparaginase and Erwinia Asparaginase * Prior transplant less than 6 months ago. * Trisomy 21 * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Pregnant or lactating patients. * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.