A Phase IIb Study of Molecular Responses to Imatinib, at Standard or Increased Doses, or Dasatinib (NSC-732517) for Previously Untreated Patients With Chronic Myelogenous Leukemia (CML) in Chronic Phase

Inclusion Criteria

Criteria:

- Diagnosis of chronic phase chronic myelogenous leukemia (CML) by bone marrow
aspiration, biopsy, and peripheral blood counts, meeting criteria for 1 of the
following:

- Philadelphia chromosome-positive* or presence of the variants of the (9;22)
translocation by cytogenetics or fluorescent in situ hybridization

- Secondary chromosomal abnormalities (in addition to the Philadelphia chromosome)
allowed; bcr-abl positive* by reverse transcription polymerase chain reaction
[Note: *First cytogenetic or molecular analysis performed within the past 180
days to confirm status]

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
stage I or II cancer currently in complete remission

- Must be enrolled on SWOG-9007 (SWOG institutions only) and SWOG-S9910

- No significant bleeding disorder unrelated to cancer including:

- Congenital bleeding disorders (e.g., von Willebrand's disease)

- Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII
antibodies)

- Bilirubin no greater than 2.0 times upper limit of normal (ULN)

- AST or ALT no greater than 2.0 times ULN

- No cardiac symptoms including any of the following:

- Uncontrolled angina

- Congestive heart failure or myocardial infarction within the past 6 months

- Diagnosed or suspected congenital long QT syndrome

- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, or Torsades de pointes)

- Prolonged QTc interval on electrocardiogram (> 450 msec)

- Uncontrolled hypertension

- Zubrod 0-2

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other concurrent anticancer biologic agents

- No prior chemotherapy for peripheral blood stem cell mobilization

- Prior collection of unmobilized peripheral blood stem cells allowed

- No other concurrent anticancer chemotherapy

- Concurrent hydroxyurea and/or anagrelide to control blood counts allowed provided it
is only administered during the first 28 days of study therapy and for no more than
28 additional days after study therapy

- No concurrent anticancer radiotherapy

- More than 28 days since prior major surgery and recovered

- No prior treatment for CML (except hydroxyurea and/or anagrelide)

- No concurrent therapeutic anticoagulation with warfarin

- Concurrent therapeutic anticoagulation with low-molecular weight heparin allowed

- Concurrent low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed
(arm III only)

- No concurrent drugs* that have a risk of causing Torsades de Pointe including (arm
III patients only):

- Quinidine

- Procainamide

- Disopyramide

- Amiodarone

- Sotalol

- Ibutilide

- Dofetilide

- Erythromycin

- Clarithromycin

- Chlorpromazine

- Haloperidol

- Mesoridazine

- Thioridazine

- Pimozide

- Cisapride

- Pepridil

- Droperidol

- Methadone

- Arsenic

- Chloroquine

- Domperidone

- Halofantrine

- Levomethadyl

- Pentamidine

- Sparfloxacin

- Lidoflazine [Note: *Patients who have discontinued any of these medications must
have a wash-out period of at least 5 days or at least 5 half-lives of the drug
prior to first dose of dasatinib]

- No concurrent drugs that irreversibly inhibit platelet function, including any of the
following (arm III only):

- Aspirin

- Patients who have discontinued aspirin must have a wash-out period of at
least 7 days for low-dose aspirin (< 325 mg/day) or 14 days for high-dose
aspirin (> 325 mg/day) prior to first dose of dasatinib

- Dipyridamole

- Epoprostenol

- Eptifibatide

- Clopidogrel

- Cilostazol

- Abciximab

- Ticlopidine

- No other concurrent anticancer agents