DISEASE CHARACTERISTICS:

• Diagnosis of blastic phase chronic myelogenous leukemia (CML), defined by ≥ 1 of the following criteria:

  • At least 30% myeloid blasts in peripheral blood or bone marrow
  • Extramedullary infiltrates of leukemic cells (other than in the spleen or liver) with peripheral blood myeloid blast morphology
• Philadelphia chromosome-positive OR BCR-ABL-positive disease

• Previously treated with imatinib mesylate AND meets 1 of the following criteria:

  • Primary* or acquired** hematologic resistance to imatinib mesylate, defined as 1 of the following:

    • Initial diagnosis of chronic phase CML that progressed to blastic phase CML during treatment with imatinib mesylate at a dose ≥ 400 mg/day
    • Initial diagnosis of accelerated phase CML that progressed to blastic phase CML during treatment with imatinib mesylate at a dose ≥ 600 mg/day ( 400-599 mg/day in patients intolerant to a dose ≥ 600 mg/day)
    • Initial diagnosis of blastic phase CML, meeting the criteria for blast crisis after ≥ 4 weeks (2 weeks for rapid disease progression) of treatment with imatinib mesylate at a dose ≥ 600 mg/day (400-599 mg/day in patients intolerant to a dose ≥ 600 mg/day) NOTE: *Disease did not respond to treatment with imatinib mesylate

NOTE: **Disease responded to treatment with imatinib mesylate but subsequently progressed to accelerated phase CML

• Intolerant to imatinib mesylate, defined as toxicity possibly related to treatment with imatinib mesylate at a dose ≤ 400 mg/day that led to discontinuation of therapy OR patient can only tolerate imatinib mesylate at doses < 400 mg/day

  • Patients who tolerate a dose of imatinib mesylate at 400 mg/day but are intolerant to higher doses are not considered intolerant to imatinib mesylate NOTE: Imatinib mesylate need not be the most recent treatment for CML prior to study entry

    • Not eligible for OR refused to undergo transplantation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

• No history of significant bleeding disorder unrelated to CML, including any of the following:

  • Congenital bleeding disorder (e.g., von Willebrand's disease)
  • Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)

Hepatic

• Bilirubin ≤ 2.0 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN
• Total calcium normal* OR
• Ionized calcium normal* NOTE: *Supplementation allowed

Cardiovascular

• No myocardial infarction within the past 6 months
• No uncontrolled angina within the past 3 months
• No congestive heart failure within the past 3 months
• No diagnosis or suspicion of congenital long QT syndrome
• No history of clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• No prolonged QTc interval (i.e., > 450 msec) on electrocardiogram determined by Bazett's correction or Fridericia correction
• No history of second or third degree heart block unless patient has a pacemaker
• No heart rate consistently < 50 beats/minute on electrocardiogram
• No uncontrolled hypertension
• No other uncontrolled or significant cardiovascular disease

Gastrointestinal

• No clinically significant gastrointestinal tract bleeding within the past 6 months
• No digestive dysfunction that would preclude study participation

Other

• Not pregnant or nursing

  • No nursing during and for ≥ 3 months after completion of study treatment
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and for ≥ 3 months after completion of study treatment
• Potassium normal*
• Magnesium normal*
• No serious uncontrolled medical disorder or active infection that would preclude study participation
• No dementia or altered mental status that would preclude giving informed consent
• No evidence of organ dysfunction that would preclude study participation
• No prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of a psychiatric or physical (e.g., infectious disease) illness
• No other incurable malignancy NOTE: *Supplementation allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 14 days since prior interferon

Chemotherapy

• More than 14 days since prior cytarabine
• Prior or concurrent hydroxyurea allowed for treatment of elevated WBC (i.e., WBC > 50,000/mm^3)

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior BMS-354825
• More than 7 days since prior imatinib mesylate
• At least 7 days since prior and no concurrent low-dose aspirin (i.e., ≤ 325 mg/day)
• At least 14 days since prior and no concurrent high-dose aspirin (i.e., > 325 mg/day)
• More than 14 days since prior targeted small molecule anticancer agents
• More than 28 days since prior investigational or antineoplastic agents

• At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent drugs that carry a risk of causing torsades de pointes, including any of the following:

  • Quinidine
  • Procainamide
  • Disopyramide
  • Amiodarone
  • Sotalol
  • Ibutilide
  • Dofetilide
  • Erythromycin
  • Clarithromycin
  • Chlorpromazine
  • Haloperidol
  • Mesoridazine
  • Thioridazine
  • Pimozide
  • Cisapride
  • Bepridil
  • Droperidol
  • Methadone
  • Arsenic
  • Chloroquine
  • Domperidone
  • Halofantrine
  • Levomethadyl
  • Pentamidine
  • Sparfloxacin
  • Lidoflazine

• At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent medication that directly inhibits platelet function (except anagrelide for thrombocytosis due to CML), including any of the following:

  • Dipyridamole
  • Epoprostenol
  • Eptifibatide
  • Clopidogrel
  • Cilostazol
  • Abciximab
  • Ticlopidine

• At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent anticoagulant (e.g., warfarin, heparin, or low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin])

  • Concurrent prophylactic low-dose warfarin for prevention of catheter thrombosis and heparin-flush for IV lines allowed
• No other concurrent therapy for CML