Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia
Condition: Chronic Myeloid Leukemia; Philadelphia-Positive Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
Intervention: Dasatinib; Imatinib
Intervention description: Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks; Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks
Intervention MeSH terms: Imatinib Mesylate; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia

Summary:

      The primary purpose of this study is to estimate the major cytogenetic response rates of
      BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome
      positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of
      400-600 mg/d.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women, 18 years of age or older.

          -  Subjects with Chronic Phase Ph+ CML.

          -  Subjects have not been treated with imatinib at a dose >600 mg/day.

          -  Subjects developed resistance to disease while receiving an imatinib dose 400-600
             mg/day.

          -  Able to tolerate imatinib at the highest dose the subject had received in the past.

          -  Demonstrate adequate renal and hepatic function.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test,
             must be using an adequate method of contraception.

        Exclusion Criteria:

          -  Women who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period for a least 1 month before and at least 3 months after the
             completion of the study.

          -  Women using a prohibited contraceptive method.

          -  Women who are pregnant or breastfeeding.

          -  Men whose sexual partners are women who are of childbearing potential, and who are
             unwilling or unable to use an acceptable method to avoid pregnancy of his partner for
             the entire study period as outlined above.

          -  Prior treatment with imatinib at a dose >600 mg/day.

          -  Subjects who have previously identified specific BCR-ABL mutations.

          -  Previous diagnosis of accelerated phase or blast crisis CML.

          -  Intolerance to imatinib at any dose.

          -  Subjects who are eligible and willing to undergo transplantation during the screening
             period.

          -  Serious uncontrolled medical disorder or active infection.

          -  Uncontrolled or significant cardiovascular disease.

          -  Uncontrolled hypertension.

          -  Dementia or altered mental status.

          -  Evidence of organ dysfunction.

          -  Use of imatinib within 7 days.

          -  Use of interferon or cytarabine within 14 days.

          -  Use of a targeted small molecule anticancer agent within 14 days.

          -  Subjects taking certain medications that are accepted to have a risk of causing
             Torsades de Pointes.

          -  Subjects taking medications that irreversibly inhibit platelet function or
             anticoagulants.

          -  Prior therapy with BMS-354825.