Arsenic Trioxide in Combination With Cytarabine in Patients With High-risk MDS and Poor-prognosis AML

This is an open-label, single institution, dose-escalation study of low-dose cytosine
arabinoside and arsenic trioxide.

Patients will receive a fixed dose of arsenic trioxide administered 0.25mg/kg/day on days
1-5 and 8-12 and ara-C administered at 5, 7.5, or 10 mg/m2 SC BID days 1-14 in repeated
cycles of 2 weeks on therapy and 2 weeks off therapy in a standard dose escalation design (1
cycle = 2 weeks on therapy + 2 weeks off therapy).

Inclusion Criteria:

- Histologic diagnosis of high-risk MDS (IPSS int-2).

- No prior cytotoxic therapy for MDS or AML (patients may have received prior therapy
with hematopoietic growth factors, immunomodulatory agents or 5-azacitidine).

Exclusion Criteria:

- Pregnant or lactating women.

- Absolute QT interval >460 msec in the presence of serum potassium and magnesium
values within the normal range.

- Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or
investigational agents.

- Uncontrolled or severe cardiovascular or pulmonary disease.