Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
Intervention: Dasatinib
Intervention description: Tablets, Oral, The dosing ranges from 50mg to a total of 240mg daily with the following 3 schedules:
5 days on, 2 days off
6 days on, 1 day off
Continuous daily dosing
Once Daily (QD) or Twice Daily (BID) dosing, Subjects will be treated until progression of disease despite escalation/reductions of dose to the level deemed safe by available data, until intolerable/unacceptable toxicity or until subject withdrawal from the study or discontinuation of the study
Intervention MeSH terms: Dasatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To determine the long term safety and tolerability of dasatinib exposure in subjects
      previously treated in CA180-002.
    

Eligibility criteria:

        This study enrolled participants with Philadelphia chromosome positive (Ph+)chronic
        myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who had demonstrated
        hematologic resistance or intolerance to imatinib mesylate (Gleevec) and had experienced
        clinical benefit (in Investigator's opinion) on protocol CA180002.

        Inclusion Criteria:

          -  Signed written informed consent

          -  Previous treatment with dasatinib on protocol CA180-002 and receiving clinical benefit
             in the opinion of the investigator

          -  Completed a minimum of 3 months on protocol CA180-002

          -  Eastern Cooperative Oncology Group (ECOG)performance status 0, 1, or 2 (See Appendix
             1)

          -  Prior history of Ph+ chronic, accelerated, or blast phase CML or Ph+ ALL

        Exclusion Criteria:

          -  Women of childbearing potential(WOCBP)who are unwilling or unable to use an acceptable
             method to avoid pregnancy for the entire study period and for up to 12 weeks after the
             study

          -  WOCBP using a prohibited contraceptive method

          -  Women who are pregnant or breastfeeding

          -  Met the criteria as defined in protocol CA180-002 for discontinuation of therapy which
             includes:

          -  Withdrawal of informed consent (subject's decision to withdraw for any reason)

          -  Any clinical adverse event, laboratory abnormality or intercurrent illness which, in
             the opinion of the investigator, indicates that continued treatment with dasatinib is
             not in the best interest of the subject

          -  Imprisonment or the compulsory detention for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness

        Medical History and Concurrent Diseases

          -  A serious uncontrolled medical disorder or active infection which would impair the
             ability of the patient to receive protocol therapy;

          -  Uncontrolled angina within 3 months

          -  Diagnosed or suspected congenital long QT syndrome

          -  Any history of clinically significant ventricular arrhythmias (such as ventricular
             tachycardia, ventricular fibrillation, or Torsades de pointes)

          -  Prolonged corrected QT(QTc) interval on pre-entry electrocardiogram (> 450 msec)

          -  Uncontrolled hypertension

          -  Dementia or altered mental status that would prohibit the understanding or rendering
             of informed consent;

          -  History of significant bleeding disorder unrelated to CML, including:

               1. Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

               2. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies)

        Physical and Laboratory Test Findings

          -  Total bilirubin ≥ 1.5 mg/dl

          -  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the
             institutional upper limits of normal

          -  Serum creatinine ≥ 1.5 times the institutional upper limits of normal

        Prohibited Therapies and/or Medications

          -  Patients currently taking drugs that are generally accepted to have a risk of causing
             Torsades de Pointes including:

               -  quinidine, procainamide, disopyramide

               -  amiodarone, sotalol, ibutilide, dofetilide

               -  erythromycins, clarithromycin

               -  chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

               -  cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
                  halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

          -  Medications that inhibit platelet function and any non-steroidal anti-inflammatory
             drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was
             granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to
             CML are eligible for this protocol