| Exclusion Criteria: | 1) Subjects with Philadelphia chromosome, and BCR-abl negative CML.
2) Subjects previously intolerant of imatinib - Part 1 (dose escalation only).
3) Overt leptomeningeal leukemia. Subjects must be free of CNS involvement for a minimum of 2 months. Subjects with symptoms of CNS involvement must have a diagnositc lumbar puncture prior to study enrollment.
4) Subjects with extramedullary disease only.
5) In part 1, no prior exposure to Src, Abl, or Src/Abl kinase inhibitors is allowed.
6) Ongoing requirement for warfarin or other OAT (Part 1 only).
7) Ongoing requirement for hydroxyurea or anagrelide (Part 1 only).
8) Graft versus Host Disease (GVHD): a) Part 1 - no previous GVHD allowed; b) Part 2 - no treated or untreated GVHD within 60 days of study start.
9) Major sugery within 14 days or radiotherapy within 7 days before the first dose of SKI-606 (recovery from any previous surgery should be complete before day 1).
10) Ongoing clinical requirement for administration of a strong inhibitor CYP-3A4 (part 1 only)
11) History of clinically significant or uncontrolled cardiac disease including: history of or active congestive heart failure; uncontrolled angina or hypertension within 3 months; myocardial infarction (within 12 months); clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); diagnosed or suspected congenital or acquired prolonged QT syndrome; unexplained syncope; history of prolonged QTc.
12) Prolonged QTc (>0.45 sec, average of triplicate readings at screening).
13) Concomitant use of or need for medications known to prolong the QT interval.
14) Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval.
15) Recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or Grade > 1 diarrhea, nausea or emesis lasting more than 2 days, despite adequate medical therapy).
16) Pregnant or breastfeeding women.
17) Evidence of serious active infection, significant medical or psychiatric illness.
18) Known seropositivity to HIV, or current acute or chronic Hepatitis B or Hepatitis C (antigen positive), cirrhosis, or clinically significant abnormal laboratory finding that would, in the investigator's judgment, make the subject inappropriate for this study. |