Treatment of Elderly Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic (MD) Syndrome With Laromustine and Infusional Cytarabine

There is no known standard chemotherapy that is considered effective for older patients with
AML or high risk MDS at this time, and with current treatment, tumor reduction can be
difficult to achieve and is short-lived. We are, therefore, interested in developing new
drugs that might have a longer-lasting effect against disease.

Laromustine is a new drug that has been shown to have anti-cancer activity in animal and
human studies. It interacts with the DNA of a cancer cell and kills the cell. Cytarabine
(AraC) is a commercially available chemotherapy drug that is active against leukemia and used
routinely when the disease is first diagnosed. In previous studies, when higher doses of
laromustine were given, laromustine and AraC achieved more responses than patients treated
with AraC alone. However, this advantage was offset by the fact that more patients given
laromustine/AraC died to due side effects. We wish to determine the effectiveness of
laromustine in combination with infusional AraC in AML and high risk MDS patients who are 60
or more years of age.

Inclusion Criteria:

- Diagnosis of AML based on WHO criteria (greater than 20% blasts in the bone marrow or
blood) excluding AML M3, acute promyelocytic leukemia OR diagnosis of high-risk MDS
defined as International Prognostic Scoring System INT-2.

- ECOG performance status equal to 0, 1, 2.

- No prior treatment for AML with myeloablative treatment. Patients may have prior
treatment with a biologic therapy. Patients with MDS or AML that has evolved from MDS
could have received prior low-dose cytotoxic therapy with agents such as azacytidine
or low-dose Ara C.

- Ability to sign an Informed Consent according to institutional guidelines.

- Patients must have the following clinical laboratory values within 24 hours prior to
beginning protocol treatment: a) serum creatinine less than or equal to 2.0mg/dl. b)
total bilirubin less than or equal to 2.0 mg/dl c) ALT or AST less than or equal to 5
times the upper limit of normal.

Exclusion Criteria:

- Uncontrolled active infection. Patients with infections who are under active treatment
with antibiotics and whose infections are controlled may be entered into the study.
Patients with chronic hepatitis are eligible.

- Active heart disease including myocardial infarction, symptomatic coronary artery
disease, arrhythmias not controlled by medication or uncontrolled congestive heart
failure.

- Severe pulmonary disease not controlled with medication.

- Patients with serum creatinine > 2.0, serum bilirubin > 2.0. ALT or AST greater that 5
times the upper limit of normal. Patients with bilirubin or creatinine outside the
acceptable levels will be considered eligible if this abnormality is clearly leukemia
related and discussed with the principal's investigator prior to enrollment.

- Patients concurrently receiving any other standard or investigational treatment for
leukemia with the exception of hydroxyurea.

- Since the formulation contains 30% ethanol, patients being treated with Antabuse
(disulfiram) are excluded from the study.

- Patients with APL t(15;17)

- Patients with ECOG performance status of 3 or 4.

- Patients should be off metronidazole (Flagyl) at least 24 hours before starting
laromustine.