Inclusion Criteria

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