Arsenic Trioxide and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (CML)

Inclusion Criteria:

* Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by fluorescent In Situ Hybridization (FISH) for BCR/ABL translocation and/or standard cytogenetics analysis.
* Participants may have received prior hydroxyurea but may not be currently being treated with hydroxyurea at the time of study initiation.
* Participants may have received prior TKI therapy, however must be on a stable dose of their current TKI for at least one month prior to enrollment.
* Participants must demonstrate evidence of persistent disease either by cytogenetics/FISH or by PCR for BCR/ABL in the peripheral blood or bone marrow.
* Greater than or equal to 18 years in age. Because little dosing or adverse event data are currently available on the use of Arsenic in participants \<18 years of age, children are excluded from this study.
* Life expectancy of greater than 3 months
* ECOG performance status \<2
* Participants must have normal organ and marrow function as defined below:

  * Bilirubin ≤ 2.0 mg/dL
  * Creatinine ≤ 2 mg/dL
  * ALT \< 2.5 X institutional upper limit of normal
  * AST \< 2.5 X institutional upper limit of normal
  * WBC \> 2.0 K/uL
  * Platelets \>100K
* Oxygen saturation \> 95% on room air
* The effects of Arsenic on the developing human fetus are unknown. For this reason, women of child-bearing potential must have a documented negative pregnancy test; in addition, agreement to use adequate contraception (hormonal or barrier method of birth control; abstinence) must be documented for both women of child-bearing potential and men prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* All patients must demonstrate the ability to understand the investigational nature of this study and must sign a written informed consent document in accordance with institutional and federal guidelines

Exclusion Criteria:

* History of acute myocardial infarction, unstable angina, congestive heart failure, or arrhythmia within the last three months
* Participants may not be receiving any other study agent
* Mean QTc\> 450 ms at time of screening
* Use of potassium wasting diuretics during study treatment
* Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. The following must be discontinued at least 7 days prior to enrollment to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
* Drugs that are highly dependent on CYP3A4 for metabolism and have a narrow therapeutic index (see Appendix A) are allowed but must be used with caution
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Concurrent and or uncontrolled psychiatric or medical condition which may interfere with the study completion.
* Pregnant women are excluded from this study because the risk of Arsenic to a developing fetus is unknown. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Arsenic, breastfeeding should be discontinued if the mother is treated on this clinical trial
* Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
* HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TKI therapy and Arsenic. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.