Pilot Trial of Arsenic + Cytarabine in Patients With Myelofibrosis

Inclusion criteria

• Patients > = 18 years with a documented history of myelofibrosis transformed to acute myeloid leukemia using the World Health Organization criteria of > = 20% blasts in the peripheral blood or bone marrow; the diagnosis of myelofibrosis could be either primary myelofibrosis (myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia), post-polycythemia vera or post-essential thrombocytosis.
• Patients > = 18 years with myelofibrosis (either primary (myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia), post polycythemia vera or post essential thrombocytosis) who 1) meet the Mayo Clinic criteria for high risk disease (> = 2 of the following criteria: hemoglobin <10 g/dL, WBC <4 or >30 x 109/L, platelets < 100 x 109/L, absolute monocyte count > = 1 x 109/L) AND 2) have failed to respond to treatment with at least one prior therapy for myelofibrosis (erythropoietic cytokines, androgens, hydrea, interferon, thalidomide, lenalidomide or investigational therapy).
• Patients must have discontinued prior myelofibrosis treatments (with the exception of hydrea, which is permitted for control of leukocytosis) for at least 14 days prior to starting study drug
• ECOG performance status of < = 2
• Serum creatinine < = 2.5 times the upper limit of normal
• Serum bilirubin < = 2.5 times the upper limit of normal
• Serum potassium >4.0 mEq/dL and serum magnesium >2.0 mg/dL. If these serum electrolytes are below the specified limits on the baseline laboratory tests, electrolytes will be administered to bring the serum concentrations to these levels before administering arsenic trioxide.
• Patients will be eligible for this trial regardless of gender, racial/ethnic background, provided all other inclusion and exclusion criteria are met and the patient or patient's legally authorized guardian signs the informed consent.

Exclusion criteria

• Pregnant or lactating women
• Presence of a (9;22) translocation cytogenetically, or presence of bcr-abl by FISH (fluorescence in situ hybridization) or PCR (polymerase chain reaction)
• Absolute QT interval >500 msec in the presence of serum potassium ≥ 4.0 mEq/L and magnesium > = 1.8 mg/dL.
• Prior cytotoxic chemotherapy for AML or MDS; prior treatment with hydroxyurea, 5-azacytidine, decitabine, thalidomide and lenalidomide are permitted. Prior treatment with low-dose cytarabine is not permitted.
• Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or investigational agents.
• Uncontrolled or severe cardiovascular, pulmonary or infectious disease or other medical condition that would prohibit use of the planned study treatments.
• Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests.