Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib
Condition: Chronic Phase Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Imatinib; Dasatinib
Intervention MeSH terms: Imatinib Mesylate; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 262.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to test the hypothesis that patients with CML who have not
      achieved optimal response after 3 months of treatment with imatinib will have a better
      response by switching to dasatinib compared to staying on their original imatinib regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but
             without one log BCR-ABL reduction (BCR-ABL level >10% IS) 3 months of imatinib 400mg
             treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed
             with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within
             the 3 month period before randomization). Imatinib monotherapy must have been started
             within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)

          -  Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment
             interruption or dose reductions are required to be on treatment with 400 mg imatinib
             for two weeks immediately prior to randomization to ensure tolerance to imatinib

          -  Eastern Co-Operative Group (ECOG) performance status = 0 - 2

          -  Adequate renal function defined as serum creatinine ≤3 times the institutional upper
             limit of normal (ULN)

          -  Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional
             ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times
             the institutional ULN

        Exclusion Criteria:

          -  Previous diagnosis of accelerated phase or blast crisis

          -  Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases at baseline bone
             marrow cytogenetic test, unless the same abnormalities were present at diagnosis.
             Patients with no evidence of clonal evolution, including those patients whose
             cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are
             eligible for the study

          -  Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after
             initial achievement

          -  Documented T315I/A, F317L, or V299L mutations (if already available - not required for
             screening)

          -  A serious uncontrolled medical disorder or active infection that would impair the
             ability of the subject to receive protocol therapy