Dasatinib in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

OBJECTIVES:

Primary

• Determine the long-term safety and tolerability of dasatinib in patients with Philadelphia chromosome-positive chronic myelogenous leukemia or acute lymphoblastic leukemia resistant or intolerant to imatinib mesylate.

Secondary

• Describe any hematologic or cytogenetic response in patients treated with this drug.
• Determine the duration of hematologic and cytogenetic response in patients using this drug during trial UCLA-0303035.
• Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: This is an open-label, roll-over study of protocol UCLA-0303035.

Patients receive oral dasatinib once or twice daily for 5, 6, or 7 days. Treatment repeats every 7 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following hematologic malignancies:

• Chronic phase chronic myelogenous leukemia (CML)

• In complete hematologic response after treatment on protocol UCLA-0303035, as indicated by the following criteria:

• WBC ≤ upper limit of normal (ULN)
• Platelet count < 450,000/mm^3
• No blasts or promyelocytes in peripheral blood
• Less than 5% myelocytes plus metamyelocytes in peripheral blood
• Peripheral blood basophils ≤ ULN
• No extramedullary involvement (including no hepatomegaly or splenomegaly)
• Response lasting ≥ 4 weeks after first documentation
• Accelerated or blastic phase CML or acute lymphoblastic leukemia

• In major hematologic response* after treatment on protocol UCLA-0303035, defined as 1 of the following:

• In complete hematologic response*, as indicated by the following criteria:

• WBC ≤ ULN
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No blasts or promyelocytes in peripheral blood
• Bone marrow blasts ≤ 5%
• Less than 5% myelocytes plus metamyelocytes in peripheral blood
• Peripheral blood basophils ≤ ULN
• No extramedullary involvement (including no hepatomegaly or splenomegaly)
• No evidence of leukemia, as indicated by the following criteria:

• WBC ≤ ULN
• No blasts or promyelocytes in the peripheral blood
• Bone marrow blasts ≤ 5%
• Less than 5% myelocytes plus metamyelocytes in peripheral blood
• Peripheral blood basophils ≤ ULN
• No extramedullary involvement (including no hepatomegaly or splenomegaly)
• Absolute neutrophil count ≥ 500/mm^3 and < 1,000/mm^3 AND platelet count ≥ 20,000/mm^3 and < 100,000/mm^3
• In minor hematologic response* after treatment on protocol UCLA-0303035, as indicated by the following criteria:

• Less than 15% in bone marrow and < 15% in peripheral blood
• Less than 30% blasts plus promyelocytes in bone marrow and < 30% blasts plus promyelocytes in peripheral blood
• Less than 20% basophils in peripheral blood
• No extramedullary disease other than spleen and liver NOTE: *Response confirmed after ≥ 4 weeks allowed provided there is no concurrent anagrelide or hydroxyurea during this time
• Philadelphia chromosome-positive (Ph+) disease
• Resistant or intolerant to prior imatinib mesylate
• Received and benefitted from ≥ 3 months of prior therapy with dasatinib on protocol UCLA-0303035

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
• No serious uncontrolled medical disorder
• No active infection that would preclude study participation
• No uncontrolled angina within the past 3 months
• No diagnosed or suspected congenital long QT syndrome
• No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• QTc ≤ 450 msec on electrocardiogram
• No uncontrolled hypertension
• No dementia or altered mental status the would prohibit the understanding or rendering of informed consent
• No history of the following significant bleeding disorders unrelated to CML:

• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
• Diagnosed acquired bleeding disorder in the past year (e.g., acquired antifactor VIII antibodies)
• Not involuntarily incarcerated for either psychiatric or physical (e.g., infectious disease) illness
• No patients who are imprisoned
• No clinical adverse event, laboratory abnormality, or intercurrent illness that may preclude study treatment, in the opinion of the investigator
• Bilirubin < 1.5 mg/dL
• ALT and AST < 2 times upper limit of normal (ULN)
• Creatinine < 1.5 times ULN

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent use of the following drugs that may confer risk of torsades de pointes:

• 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
• No other concurrent treatment for CML except for hydroxyurea for a 2-week duration
• No concurrent medications that inhibit platelet function (e.g., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, or any nonsteroidal anti-inflammatory drug)* except for hydroxyurea or anagrelide
• No concurrent anticoagulants (e.g., warfarin or heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin]) except as prophylaxis for catheter thrombosis and/or heparin flushes for IV lines* NOTE: *Allowed if received previously on UCLA-0303035