Nilotinib as First-line Treatment of Ph+ CML in Early Chronic Phase

Exclusion Criteria

• •Impaired cardiac function, including LVEF \< 45% as determined by MUGA scan or echocardiogram, uncontrolled congestive heart failure, uncontrolled hypertension
• •History of myocardial infarction within three months, or uncontrolled angina pectoris.
• •Significant electric heart abnormalities, including history or presence of significant ventricular or atrial tachyarrhythmias, congenital long QT syndrome and/or QTc \> 450 msec on screening ECG (using the QTcF formula).
• •Patients with ventricular pacemakers and clinically significant bradycardias.
• •Patients with heart blocks.
• •History of acute or chronic pancreatitis.
• •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• •Use of therapeutic coumarin derivates (i.e. warfarin, acenocoumarol, phenprocoumon).
• •Acute or chronic liver or renal disease considered unrelated to leukaemia
• •Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
• •Patients who are currently receiving treatment with any of the medications listed in Appendix E and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT, with the exception of HU and Anagrelide.
• •Patients who have received any antileukemic agents and treatments, including HSCT, with the exception of HU and Anagrelide.
• •Patients who have received any investigational drug ≤ 4 weeks.
• •Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• •Patients 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 administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
• •Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) 1 week prior to starting study drug.
• •Patients who have received immunotherapy 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
• •Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
• •Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
• •Patients unwilling or unable to comply with the protocol.