This phase II trial studies how well arsenic trioxide works in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. Determine the complete remission rate of relapsed and refractory acute myeloid leukemia (AML) patients with Mutated Nucleophosmin 1 (NPM1) gene.

SECONDARY OBJECTIVES:

I. Determine the duration of remission in these patients. II. Determine the in vivo biological effect of arsenic trioxide in AML with mutated NPM1.

OUTLINE:

Patients receive arsenic trioxide intravenously (IV) over 1-2 hours daily for up to 45 days. Patients achieving complete remission, receive arsenic trioxide IV over 1-2 hours daily 5 days a week for 4 weeks. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

• AML, any French- American- British (FAB) subtype except M3, with confirmed mutation in the NPM1 gene
• Relapsed and/or refractory AML from any duration of complete remission (CR); any number of prior therapies allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2, life expectancy > 3 months
• Serum creatinine =< 2.0 mg/dL
• Bilirubin =< 2.0 mg/dL
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in women; sexually active males or females may not participate unless they have agreed to use an effective contraceptive method
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anti-cancer agents
• Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Known hypersensitivity to arsenic trioxide