A Phase l/ll Study of AMN107 in Adult Patients With Glivec-intolerant CML or Relapsed-refractory Ph+ALL

Inclusion Criteria:

• Diagnosed as Ph+ ALL who are either relapsed after or refractory to standard therapy
• Diagnosed as CML in blast crisis or accelerated phase or chronic phase who areresistant or intolerant to imatinib
• Performance status is normal or ambulatory and capable of all self-care ExclusionCriteria
• A history of significant or serious uncontrolled cardiovascular disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of nilotinib
• Patients who are pregnant or breast feeding, or adults of reproductive potential notemploying an effective method of birth control

Exclusion Criteria:

• Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNSinvolvement, lumbar puncture is not required
• Impaired cardiac function, including any one of the following
• LVEF < 45% as determined by echocardiogram
• Complete left bundle branch block
• Use of a cardiac pacemaker
• ST depression of > 1mm in 2 or more leads and/or T-wave inversions in 2 or morecontiguous leads
• Congenital long QT syndrome
• History of or presence of significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (< 50 beats per minute)
• QTc > 480 msec on screening ECG (using the QTcF formula)
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• Myocardial infarction within 3 months prior to starting AMN107
• Uncontrolled angina pectoris
• Other clinically significant heart disease (e.g., congestive heart failure,uncontrolled hypertension, history of labile hypertension, or history of poorcompliance with an antihypertensive regimen)
• Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of AMN107 (e.g. ulcerative diseases, uncontrolled nausea,vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Use of therapeutic warfarin
• Acute or chronic liver or renal disease considered unrelated to tumor (e.g.,hepatitis, cirrhosis, renal insufficiency, etc.)
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolleddiabetes, active or uncontrolled infection) that could cause unacceptable safety risksor compromise compliance with the protocol
• Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1week prior to starting study drug.
• Patients who are currently receiving treatment with any of the medications listed in (cf. Post-text suppl. 5) that cannot be either discontinued or switched to a differentmedication prior to starting study drug. The medications listed in (cf. Post-textsuppl. 5) have the potential to prolong the Q-T interval.
• Patients who have received chemotherapy ≤ 1 week or who are within 5 half-lives oftheir last dose chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to startingstudy drug or who have not recovered from side effects of such therapy. Hydroxyurea ispermitted at the investigator's discretion prior to enrollment.
• Patients who have received Glivec® ≤ 1 week or who have not recovered from sideeffects of such therapy.
• Patients who have received immunotherapy ≤ 1 week prior to starting study drug or whohave not recovered from side effects of such therapy.
• Patients who have received any investigational drug (excluding STI571/Glivec) ≤ 4weeks or investigational cytotoxic agent within 1 week (or who are within 5 half-livesof a previous investigational cytotoxic agent) prior to starting study drug or whohave not recovered from side effects of such therapy.
• Patients who have received wide field radiotherapy ≤ 4 week or limited field radiationfor palliation ≤ 2 week prior to starting study drug or who have not recovered fromside effects of such therapy.
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug orwho have not recovered from side effects of such therapy.
• Patients who are pregnant or breast feeding, or adults of reproductive potential notemploying an effective method of birth control. (Women of childbearing potential musthave a negative serum pregnancy test within 48 hrs prior to administration of AMN107).Post-menopausal women must be amenorrheic for at least 12 months to be considered ofnon-childbearing potential. Male and female patients must agree to employ an effectivebarrier method of birth control throughout the study and for up to 3 months followingdiscontinuation of study drug
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is notmandatory)
• Patients with a history of another primary malignancy that is currently clinicallysignificant or currently requires active intervention.
• Patients unwilling or unable to comply with the protocol Other protocol-defined inclusion and exclusion criteria may apply.