This is an open-label, one arm, single institution study. Arsenic trioxide [TrisenoxTM
Injection], 0.25mg/kg/dose administered intravenously over 2 hours.
Complete remission, partial remission, clinical improvement, progressive disease, stable
disease, relapse (per IWG consensus criteria, 2006) Clinical chemistry, hematology and ECGs
will be assessed at least weekly during study treatments. Adverse events will be assessed in
accordance with the NCI Common Toxicity Criteria, Version 2 at each study visit.
1. 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.
2. 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
3. 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
4. ECOG performance status of < = 2
5. Serum creatinine < = 2.5 times the upper limit of normal
6. Serum bilirubin < = 2.5 times the upper limit of normal
7. 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.
8. 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.
1. Pregnant or lactating women
2. Presence of a (9;22) translocation cytogenetically, or presence of bcr-abl by FISH
(fluorescence in situ hybridization) or PCR (polymerase chain reaction)
3. Absolute QT interval >500 msec in the presence of serum potassium ≥ 4.0 mEq/L and
magnesium > = 1.8 mg/dL.
4. 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.
5. Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or
6. Uncontrolled or severe cardiovascular, pulmonary or infectious disease or other
medical condition that would prohibit use of the planned study treatments.
7. Inability or unwillingness to comply with the treatment protocol, follow-up, or