T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)
T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)
Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating
 children (age 1-21) with leukemia. This research study will use clofarabine with two other
 cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and
 cyclophosphamide (Cytoxan®).
Clofarabine, etoposide and cyclophosphamide have been used together in a phase I study to
 find out the highest doses of these drugs that can be safely given to children with relapsed
 or refractory leukemia. This study is a phase II study which will use the drugs to study how
 well these drugs work against AML. This study will also examine the safety of this drug
 combination.
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.