Gleevec as Maintenance Therapy After Cytogenetic Response With Nilotinib in Newly Diagnosed Chronic Myelogenous Leukemia

Prior treatment

• Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol) up to day before study drug administration
• Other concurrent severe and/or uncontrolled medical conditions
• Pts who have received any investigational drug ≤4 weeks or investigational cytotoxic agent within 1 week (or who are within 5 half-lives of a previous investigational cytotoxic agent) prior to starting study drug or who have not recovered from side effects of such therapy
• Pts who have received wide field radiotherapy ≤4 weeks or limited field radiation for palliation \<2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Pts who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

Other illness

• Acute or chronic liver or renal disease considered unrelated to tumor such as active Hepatitis A, B, or C
• Known diagnosis of HIV
• Pt with a history of another malignancy that is currently clinically significant or currently requires active intervention

Lab values

• Impaired cardiac function, including any one of the following:
  • Left ventricle ejection fraction (LVEF) \<45% or below the institutional lower limit of the normal range (whichever is higher) as determined by MUGA scan or echocardiogram
  • Complete left bundle branch block
  • Use of a pacemaker
  • ST depression of \>1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads
  • Congenital long QT syndrome
  • History of or presence of significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (\<50 beats/min)
  • QTc \>450 msec on screening ECG
  • Right bundle branch block plus left anterior hemiblock, bifascicular block
  • Myocardial infarction within 12 months prior to starting nilotinib
  • Unstable angina diagnosed or treated during the past 12 months
  • Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, or history of labile hypertension)
• Pts who are currently receiving treatment with any of the medications that have the potential to prolong QT interval
• Pts who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to drug administration). Post menopausal women must be amenorrheic for at least 12 months. Male \& female pts must agree to employ an effective method of birth control throughout the study and for 3 months following discontinuation of study drug

Other

• Cytopathologically confirmed central nervous system (CNS) infiltration
• Pts unwilling or unable to comply with protocol

• Newly diagnosed untreated Philadelphia chromosome-positive CML (use of hydroxyurea for \<3 months is allowed) in chronic phase defined with the following criteria:
  • \<15% blasts in peripheral blood (PB) \& bone marrow (BM)
  • \<30% blasts plus promyelocytes in PB \& BM
  • \<20% basophils in PB
  • ≥100 x 109/L platelets
  • No evidence of extramedullary involvement, with the exception of liver \& spleen
• Patients (pts) ≥18 yrs of age
• WHO Performance Status of ≤2
• Pts must have the following laboratory values:
  • Potassium within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication
  • Total calcium (corrected for serum albumin) and magnesium within normal limits or correctable with supplements
  • Phosphorus ≥ lower limit of normal (LLN) or correctable with supplements
  • ALT and AST ≤2.5 x upper limit of normal (ULN) or ≤5.0xULN if considered due to tumor
  • Alkaline phosphatase ≤2.5xULN
  • Serum bilirubin ≤1.5xULN
  • Serum Cr ≤1.5xULN or 24-hour Cr Cl ≥50 ml/min
  • Serum amylase ≤1.5xULN and serum lipase ≤1.5xULN
• Written signed informed consent prior to any study procedures