INCLUSION CRITERIA:

• Diagnosis of Philadelphia chromosome positive, chronic phase chronic myelogenous leukemia (CML) meeting all of the following criteria*:
• Less than 15% blasts in peripheral blood and bone marrow
• Less than 20% basophils in peripheral blood
• Less than 30% blasts and promyelocytes in peripheral blood and bone marrow
• Platelet count at least 100,000/mm^3 NOTE: *Patients who previously met the criteria for accelerated phase or blast phase CML, responded to treatment, and currently meet the criteria for chronic phase CML are eligible
• Primary or acquired hematologic resistance to imatinib mesylate OR intolerance to imatinib mesylate defined as follows:

• Primary hematologic resistance is defined as failure to reach complete hematologic response (CHR) with a dose of 400 mg/day continued for at least 3 months

  • Patients with hematological progression (i.e., WBC at least 10,000/mm^3 and rising consistently on at least 2 consecutive measurements obtained at least 14 days apart) while receiving imatinib mesylate of 400 mg/day are eligible if they have received less than 3 months of therapy

• Acquired hematologic resistance is defined as achieving a CHR, but subsequently developing a rising WBC to at least 10,000/mm^3

  • WBC must be at least 10,000/mm^3 and rising on at least 2 measurements obtained at least 14 days apart with at least 1 of these measurements greater than 15,000/mm^3

• Intolerance is defined as having discontinued imatinib mesylate due to nonhematologic toxicity of any grade

  • CD4^+ T-cell count at least 350/mm^3
• 18 and over
• ECOG 0-1
• Life expectancy, At least 6 months.

• Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • ALT and AST no greater than 2.0 times upper limit of normal (ULN)

• Renal

  • Creatinine no greater than 1.5 times ULN
  • Potassium normal*
  • Magnesium normal*
  • Serum calcium or ionized calcium at least lower limit of normal NOTE: *Patients with low levels may be repleted to be eligible
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and 1 month after study participation
• More than 14 days since prior interferon
• More than 14 days since prior cytarabine
• More than 3 days since prior hydroxyurea
• More than 28 days since other prior investigational or antineoplastic agents
• More than 7 days since prior imatinib mesylate
• At least 5 days or 5 half-lives since prior medications that inhibit platelet function, including the following:
• Aspirin
• Dipyridamole
• Epoprostenol
• Eptifibatide
• Clopidogrel
• Cilostazol
• Abciximab
• Ticlopidine
• At least 5 days or 5 half-lives since prior anticoagulants such as warfarin or heparin/low molecular weight heparin (e.g., danaparoid, dalteparin, tinzaparin, enoxaparin)
• At least 5 days or 5 half-lives since prior drugs accepted to have a risk of causing torsades de pointes, including the following:
• Class IA antiarrhythmic agents (e.g., quinidine, procainamide, or disopyramide)
• Class III antiarrhythmic agents (e.g., amiodarone, sotalol, ibutilide, or dofetilide)
• Macrolide antibiotics (e.g., erythromycin or clarithromycin)
• Antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, or pimozide)
• Tricyclic antidepressants
• Cisapride
• Bepridil
• Inapsine
• Methadone
• Arsenic
• Concurrent anagrelide for thrombocytosis due to CML allowed

Exclusion Criteria:

• extramedullary involvement (other than liver or spleen)
• significant bleeding disorder unrelated to CML
• acquired bleeding disorder within the past year (e.g., acquired antifactor VIII antibodies)
• congenital bleeding disorders (e.g., von Willebrand disease)
• uncontrolled or significant cardiovascular disease
• uncontrolled angina within the past 6 months
• congestive heart failure within the past 6 months
• myocardial infarction within the past 12 months
• history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• history of second or third degree heart block (may be eligible if patient has a pacemaker)
• diagnosed or suspected congenital long QT syndrome
• prolonged QTc interval on pre-entry EKG (i.e., greater than 450 msec)
• heart rate less than 50/minute on pre-entry EKG
• uncontrolled hypertension
• vasculitis
• pregnant or nursing
• gastrointestinal tract bleeding within the past 6 months
• connective tissue disorders
• other serious uncontrolled medical disorder or active infection that would impair the ability to receive study therapy
• dementia or altered mental status that would preclude giving informed consent
• evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML
• prisoners or patients who are compulsorily detained (e.g., involuntary incarceration for treatment of either a psychiatric or physical [e.g., infectious disease] illness)
• concurrent drugs accepted to have a risk of causing torsades de pointes
• other concurrent treatment for CML
• concurrent dolasetron or droperidol
• concurrent anticoagulants
• concurrent medications that inhibit platelet function