DISEASE CHARACTERISTICS:

• 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
  • No extramedullary involvement (other than liver or spleen) 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• See Disease Characteristics
• No significant bleeding disorder unrelated to CML
• No acquired bleeding disorder within the past year (e.g., acquired antifactor VIII antibodies)
• No congenital bleeding disorders (e.g., von Willebrand disease)

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

Cardiovascular

• No uncontrolled or significant cardiovascular disease
• No uncontrolled angina within the past 6 months
• No congestive heart failure within the past 6 months
• No myocardial infarction within the past 12 months
• No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• No history of second or third degree heart block (may be eligible if patient has a pacemaker)
• No diagnosed or suspected congenital long QT syndrome
• No prolonged QTc interval on pre-entry EKG (i.e., greater than 450 msec)
• No heart rate less than 50/minute on pre-entry EKG
• No uncontrolled hypertension
• No vasculitis

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and 1 month after study participation
• No gastrointestinal tract bleeding within the past 6 months
• No connective tissue disorders
• No other serious uncontrolled medical disorder or active infection that would impair the ability to receive study therapy
• No dementia or altered mental status that would preclude giving informed consent
• No evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML
• No prisoners or patients who are compulsorily detained (e.g., involuntary incarceration for treatment of either a psychiatric or physical [e.g., infectious disease] illness)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 14 days since prior interferon

Chemotherapy

• More than 14 days since prior cytarabine
• More than 3 days since prior hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• See Disease Characteristics
• 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
• No concurrent drugs accepted to have a risk of causing torsades de pointes
• No other concurrent treatment for CML
• No concurrent dolasetron or droperidol
• No concurrent anticoagulants
• No concurrent medications that inhibit platelet function
• Concurrent anagrelide for thrombocytosis due to CML allowed