BMS-354825 in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Is Resistant to Imatinib Mesylate

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