Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)
Condition: Leukemia, Myeloid, Chronic Phase
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Imatinib mesylate
Intervention description: Imatinib is packaged in bottles as 100mg and 400mg tablets
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 476.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: CML; Philadelphia positive; Bcr-abl; imatinib mesylate; Chronic myeloid leukemia (CML) in chronic phase

Summary:

      This study investigated the safety and efficacy of 400mg Versus 800mg imatinib in patients
      with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP)
      using molecular endpoints.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients within 6 months of diagnosis (date of initial diagnosis is the date of first
             cytogenetic analysis)

          -  Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic
             confirmation of Philadelphia chromosome of (9;22) translocations and presence of
             Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl)

          -  Documented chronic phase CML

          -  Adequate end organ function as defined by:

               -  total bilirubin < 1.5 x Upper Limit of Normal (ULN)

               -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
                  transaminase (SGPT) < 2.5 x ULN

               -  creatinine < 1.5 x ULN

        Exclusion Criteria:

          -  Patients in late chronic phase, accelerated phase, or blastic phase are excluded

          -  Patients who have received other investigational agents

          -  Patients who received Gleevec/Glivec for any duration prior to study entry, with the
             exception of those patients successfully completing [CSTI571A2107 (NCT00428909)] study
             immediately prior to the participation in this study

          -  Patient received any treatment for CML prior to study entry for longer than 2 weeks
             with the exception of hydroxyurea and/or anagrelide

          -  Patients with another primary malignancy except if the other primary malignancy is
             neither currently clinically significant or requiring active intervention

          -  Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential
             without a negative pregnancy test prior to baseline and (d) male or female of
             childbearing potential unwilling to use barrier contraceptive precautions throughout
             the trial (post-menopausal women must be amenorrheic for at least 12 months to be
             considered of non-childbearing potential).

          -  Patient with a severe or uncontrolled medical condition (i.e., uncontrolled
             diabetes,chronic renal disease)

          -  Patient previously received radiotherapy to ≥ 25% of the bone marrow

          -  Patient had major surgery within 4 weeks prior to study entry, or who have not
             recovered from prior major surgery

          -  Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥
             3

          -  Patients with International normalized ratio (INR) or partial thromboplastin time
             (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral
             anticoagulants

          -  Patients with known positivity for human immunodeficiency virus (HIV); baseline
             testing for HIV is not required

          -  Patients with identified sibling donors where allogeneic bone marrow transplant is
             elected as first line treatment

        Other protocol-defined inclusion/exclusion criteria applied.