Nilotinib as First-line Treatment of Ph+ CML in Early Chronic Phase (CML0307)

Inclusion Criteria:

• Patients with a cytologic and cytogenetic confirmed diagnosis of Ph+ CML.
• Age ≥ 18 years old
• Early CP (within 6 months from diagnosis)
• No prior treatment with any antileukemic drugs with the exception of Hydroxyurea (HU) and Anagrelide.
• WHO performance status of ≤ 2
• Normal serum level of potassium, total calcium corrected for serum albumin, magnesium and phosphorus, or correctable with supplements
• ALT and AST ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia.
• Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukemia.
• Serum bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN.
• Written informed consent prior to any study procedures being performed.

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.