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

Phase I/II Study of Arsenic Trioxide in Combination With Cytosine Arabinoside in Patients With High-risk Myelodysplastic Syndrome and Poor-prognosis Acute Myelogenous Leukemia

The purpose of this study is to find out the effectiveness and side effects of arsenic trioxide in combination with low-dose ara-C.

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.