Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)

A Randomized Open-label Study of 400 mg Versus 800 mg of Imatinib Mesylate in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints.

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.

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.