T2007-002 A Phase II Study of Clofarabine With Etoposide and Cyclophosphamide in Relapsed/Refractory AML (IND 104,650)

Inclusion Criteria:

- Age: patients must be ≥ 1 and ≤ 21 years of age at the of study entry.

- Diagnosis:

- Patients must have a diagnosis of first or second relapse or refractory acute
myelogenous leukemia (AML) according to WHO classification with ≥ 5% blasts in
the bone marrow, with or without extramedullary disease. (See Appendix I)

- Patients may have CNS 1 or CNS 2 disease but not CNS 3.

- Performance Level: Karnofsky > 50% for patients > 16 years of age and Lansky > 50%
for patients ≤ 16 years of age.

- Prior Therapy:

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

- Patient has not received more than 2 previous induction attempts. (Frontline
therapy is included in this count).

- Patients must have adequate venous access.

- At least 1 year must have elapsed since hematopoietic stem cell transplant
(HSCT) and patients must not have active GVHD.

- Reproductive Function

- Female patients of childbearing potential must have a negative serum pregnancy
test confirmed within 2 weeks 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
and for a minimum of 6 months after study treatment.

- Renal and Hepatic Function:

Patient must have adequate renal and hepatic functions as indicated by the following
laboratory values:

- Patients must have a normal calculated creatinine clearance.

- Total bilirubin <1.5 x ULN for age and conjugated/direct serum bilirubin ≤ ULN for
age if total bilirubin is elevated.

- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN.

- Alkaline phosphatase ≤ 2.5 × ULN.

- Informed Consent: Patients and/or their parents or legal guardians must be
capable of understanding the investigational nature, potential risks and
benefits of the study. All patients and/or their parents or legal guardians must
sign a written informed consent.

- Protocol Approval: All institutional, FDA, and OHRP requirements for human
studies must be met.

Exclusion Criteria:

- Patients with Down Syndrome.

- Prior treatment with Clofarabine.

- Previous history of veno-occlusive disease (VOD) or findings consistent with a
diagnosis of VOD, defined as: conjugated serum bilirubin > 1.4 mg/dL AND unexplained
weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right
upper quadrant pain without another explanation, OR reversal of portal vein flow on
ultrasound, OR pathological confirmation of VOD on liver biopsy.

- Patients who have a history of cirrhosis of the liver or who are positive for
hepatitis B core antibody (anti-HBc) or have a positive test for hepatitis C antibody
(anti-HCV).

- Patient has received TBI.

- If it has been less than 1 year since the patient had a HSCT.

- Infection Criteria

- 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).

- Positive blood culture within 48 hours of study registration.

- Patient required supplemental oxygen or vasopressors within 48 hours of study
(Oxygen after anesthesia for procedures is ok).

- Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy,
or immunotherapy other than as specified in the protocol.

- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
before planned drug initiation with the exception of hydroxyurea or intrathecal
therapy given with the diagnostic lumbar puncture.

- 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.

- Pregnant or lactating patients.

- Any 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.

- Have had a diagnosis of another malignancy, unless the patient has been disease-free
for at least 3 years following the completion of curative intent therapy with the
following exceptions:

- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible
for this study if definitive treatment for the condition has been completed.

- Patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values are also
eligible for this study if hormonal therapy has been initiated or a radical
prostatectomy has been performed.