Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia

Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML).
Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49
patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in
stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on
success of clearing MRD, proceeding to transplant within 42 days and without excessive
toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients
enrolled.

Inclusion Criteria:

- Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with
<5% blasts in the bone marrow (M1) by morphology and that meets one of the following
criteria:

- Flow cytometric evidence of MRD (≥ 0.1% leukemic blasts for ALL or <5% leukemic
blasts for AML detected in the bone marrow) OR

- Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed
within 7 days

- AND with the intent of going on to an allogeneic hematopoietic cell
transplantation (allo-HCT) independent of this study

- Age 0 to 60 years

- Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play
Score ≥ 50 for patients under 16 years of age

- Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling
investigator

- Have acceptable organ function as defined within 7 days of study registration:

- Renal: creatinine clearance ≥70mL/min/1.73m2 or serum creatinine based on
age/gender

- Hepatic: aspartate aminotransferase (ALT) < 5 x upper limit of normal (ULN) and
total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age

- Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram (ECHO/MUGA)

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14
days must have elapsed from prior chemotherapy; at least 7 days must have elapsed
since receiving biological therapy.

Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth
factor and at least 14 days since pegfilgrastim (Neulasta®) administration.

- Sexually active females of child bearing potential must agree to use adequate
contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],
surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration
of treatment and for 2 months after the last dose of chemotherapy. Sexually active men
must agree to use barrier contraceptive for the duration of treatment and for 2 months
after the last dose of chemotherapy.

- Voluntary written consent before performance of any study-related procedure not part
of normal medical care, with the understanding that consent may be withdrawn by the
subject at any time without prejudice to future medical care

Exclusion Criteria:

- Acute Promyelocytic Leukemia (APL)

- Active central nervous system (CNS) leukemia or known chloromatous disease

- Receiving or plans to receive concomitant chemotherapy, radiation therapy;
immunotherapy or other anti-cancer therapy other than is specified in the protocol

- 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. The agents used in this study are known to be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk. All
females of childbearing potential must have a blood test or urine study within 2 weeks
prior to registration to rule out pregnancy.

- Known allergy to any of the agents or their ingredients used in this study