Phase II Clofarabine and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia

The primary objective of this prospective study is to evaluate the efficacy (i.e., complete
response rate) of clofarabine and cytarabine as second course therapy for the treatment of
AML. The secondary objectives are to assess the treatment-related toxicities, to determine
the overall and relapse-free survival for patients with AML who are treated with this
regimen, and to evaluate potential factors that are predictive of response.

The investigational nature and objective of this study, the procedures involved and their
associated risks, potential benefits, and potential alternative therapies will be explained
to the patient, and a signed informed consent document will be obtained. Once consented,
eligible patients will be treated by the acute leukemia service on the University of
Pittsburgh Cancer Institute inpatient unit.

Prior to the start of chemotherapy, patients will receive dexamethasone and ondansetron as
pre-medication. Clofarabine will then be administered as intravenous infusion on days 1
through 5. Patients will be monitored closely with vital signs. Cytarabine will then be
given as intravenous infusion, starting 3 (maximum of 4) hours after the completion of
clofarabine administration on days 1 through 5.

Inclusion Criteria:

1. Patients with newly diagnosed AML based on the World Health Organization
classification who have persistent disease after their first course treatment with an
anthracycline and cytarabine

2. Able to understand and have the ability to provide written informed consent

3. Patients over 18 years of age

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

5. Left ventricular ejection fraction (LVEF) ≥ 50%

6. Negative urine pregnancy test for all females

7. All subjects must agree to use an effective method of contraception while receiving
the study drugs

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia

2. Relapsed AML

3. Prior use of clofarabine

4. Previous allogeneic or autologous hematopoietic cell transplantation

5. Impaired liver function (serum total bilirubin > 2.0 mg/dL, alanine aminotransferase
and aspartate aminotransferase ≥ 4 x the upper limit of normal)

6. Impaired renal function (serum creatinine ≥ 2.0 mg/dL)

7. Uncontrolled or life-threatening infection that is not responding to antimicrobial
therapy

8. History of a psychiatric disorder which may compromise compliance with the protocol
or which does not allow for appropriate informed consent

9. Concurrent active malignancy; exceptions include patients who have been disease free
for 5 years, patients with a history of completely resected non-melanoma skin cancer
or successfully treated in situ carcinoma, or patients with another malignancy that
is indolent or definitively treated

10. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory or cardiac disease)