| Exclusion Criteria: | 1) PHASE I: Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS involvement, lumbar puncture is not required.
2) Impaired cardiac function, including any one of the following
3) LVEF < 45% or below institutional lower limit of the normal range (which ever is higher) as determined by MUGA scan or echocardiogram.
4) Complete left bundle branch block.
5) Use of a cardiac pacemaker.
6) ST depression of > 1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads.
7) Congenital long QT syndrome.
8) History of or presence of significant ventricular or atrial tachyarrhythmias.
9) Clinically significant resting bradycardia (< 50 beats per minute).
10) QTc > 450 msec on screening ECG (using the QTcF formula)
11) Right bundle branch block plus left anterior hemiblock, bifascicular block.
12) Myocardial infarction within 3 months prior to starting AMN107.
13) Unstable angina diagnosed or treated during the past 12 months.
14) Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
15) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
16) Use of therapeutic warfarin.
17) Acute or chronic liver or renal disease considered unrelated to tumor.
18) 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.
19) Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF)less than or equal to 1 week prior to starting study drug. Erythropoietin is allowed.
20) Patients who are currently receiving treatment with any of the medications listed in post-text supplement 4 Amendment 8 and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in post-text supplement 4 Amendment 8 have the potential to prolong the QT interval or are CYP3A4 inhibitors.
21) Patients who have received chemotherapy less than or equal to 1 week (6 weeks for nitrosurea or mitomycin-C) or who are within 5 half-lives of their last dose chemotherapy dose prior to starting study drug or who have not recovered from side effects of such therapy.
22) Patients who have received imatinib less than or equal to 1 week or who have not recovered from side effects of such therapy.
23) Patients who have received immunotherapy less than or equal to 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
24) Patients who have received any investigational drug less than or equal to 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.
25) Patients who have received wide field radiotherapy less than or equal to 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.
26) Patients who have undergone major surgery less than or equal to 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
27) 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 AMN107). 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.
28) Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
29) Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
30) Patients unwilling or unable to comply with the protocol.
31) PHASE II: Cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture is not required).
32) Impaired cardiac function, including any one of the following: · LVEF < 45% as determined by MUGA scan or 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 more contiguous 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) ·
33) #32 Continued 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 poor compliance with an antihypertensive regimen).
34) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
35) Use of therapeutic warfarin.
36) Acute or chronic liver or renal disease considered unrelated to tumor.
37) 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.
38) Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) </= 1 week prior to starting study drug. Erythropoietin is allowed.
39) Patients who are currently receiving treatment with any of the medications listed in Post-text supplement 4 and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Post-text supplement 4 have the potential to prolong the QT interval.
40) Patients who have received chemotherapy </= 1 week or who are within 5 half-lives of their last dose of chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy. Hydroxyurea is permitted at the investigators discretion prior to enrollment. Patients who have received imatinib </= 5 days prior or who have not recovered from side effects of such therapy.
41) Patients who have received immunotherapy </=1 week prior to starting study drug or who have not recovered from side effects of such therapy.
42) Patients 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.
43) Patients 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.
44) Patients who have undergone major surgery </= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
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Criteria truncated, please contact Prinicipal Investigator's office for full criteria |