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

Study Overview
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Brief Summary
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RATIONALE: Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects of dasatinib in treating patients with chronic myelogenous leukemia or acute lymphoblastic leukemia.

Detailed Description
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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.

Official Title
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Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Subjects Who Experienced Clinical Benefit on Protocol CA 180-002

Conditions
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Leukemia

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib<br> | Drug: dasatinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term safety and tolerability |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent adult acute lymphoblastic leukemia, chronic myelogenous leukemia, BCR-ABL1 positive