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.