T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)

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.

      - 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.

      - Pediatric Population (age <18): Calculated creatinine clearance ≥ 90
      ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular
      filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine
      (mg/dl). k is a proportionality constant which varies with age and is a function
      of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of
      age; 0.55 children and adolescent girls; and 0.70 adolescent boys.

      - Adult Population (age ≥18): Serum creatinine ≤1.0 mg/dL; if serum creatinine >1.0
      mg/dL, then the estimated glomerular filtration rate (GFR) must be >60
      mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease
      equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x
      (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black.

   - 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.

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.