Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for
adolescent/young adult patients.

- Lansky Performance Index > 50 for pediatric patients less than age 10 years.

- Laboratory values obtained < 7 days prior to receiving study treatment:

- Total bilirubin < 1.5 mg/dL unless elevated due to hemolysis. The conjugated serum
bilirubin prior to study entry must be within the normal range.

- Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 × upper limit of
normal (ULN)

- Serum creatinine < 1.0 mg/dL in adolescent/young adults (patients 12 to 17 years of
age). For pediatric patients with serum creatinine above the ULN, creatinine clearance
> 90 ml/min/1.73m2 calculated using the Schwartz formula may be enrolled. Collected
creatinine clearance may be substituted.

Patients 18 years and older (Adult population): 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

- Cardiac function must be normal per the institution normal as measured by
echocardiogram (ECHO) within 7 days.

- Patients should have no evidence of myositis as detected by abnormal serum creatine
kinase and/or myoglobin.

Exclusion Criteria:

- No chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of
study drug except for 5-azacytidine, thalidomide, hydroxyurea, imatinib (Gleevec), and
interferon which must be discontinued at least 3 days before study entry and the
patient should have recovered from the toxic side effects of such therapy. In the
instance of progressive disease, anti-leukemia therapy may have been administered
within the 2-week period as long but the subject should have recovered from the toxic
effects of that therapy. Also, intrathecal therapy may be administered within the
2-week period for subjects with CNS disease.

- Patients who have had an allogeneic or autologous hematopoietic stem cell transplant.

- Patients must have discontinued all growth factors, except Procrit (epoetin), at least
1 week before study.

- Patients with known HIV positive status or AIDS.

- Patients with known active Hepatitis B, Hepatitis C or cirrhosis.

- History of severe coronary artery disease, including myocardial infarction within the
previous 3 months, arrhythmias other than atrial flutter or fibrillation requiring
medication, or uncontrolled congestive heart failure.

- Patients with active uncontrolled infection, fever of infection, or evidence for
progressive disease by CT scans of the lungs, sinuses, or abdomen. Patients who are on
antimicrobial therapy and stable, CT scans must have been stable for 4 weeks, may be
enrolled but there must be no evidence of an active infection. Patients with fever due
to leukemia may be enrolled.

- Pregnant or lactating patients. Female patients of childbearing potential must have a
negative serum pregnancy test within 14 days before study entry.