| Exclusion Criteria: | 1) Pts recv'g any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 21 days of first receipt of study drug with the exception of hydroxyurea (HU) in Stratum A pts who need to continue this agent to maintain WBC count </= 100,000/mm3. Every effort should be made to discontinue HU therapy during Cycle 1 of RO5045337. If HU discontinuation is not medically feasible during Cycle 1, these patients will not be permitted to continue Cycle 2 of RO5045337 and will be terminated from the study due to insufficient therapeutic response.
2) Patients with pre-existing GI disorders that may interfere with proper absorption of the drug(s), as per investigator's discretion.
3) Patients with history of allergic reactions attributed to components of the formulated product.
4) Patients with history of seizure disorders or CNS leukemia.
5) Patients with QTc prolongation: Men > 450 msec, Women > 470 msec), symptomatic CHF; unstable angina pectoris, cardiac arrhythmia.
6) Patients with a history of a long QT syndrome.
7) Patients recv'g CYP3A4 substrates and inhibitors within 7 days prior to the 1st dose of RO5045337, or recv'g CYP3A4 inducers within 14 days prior to the first dose of RO5045337. Every effort should be made to disc. use of the CYP3A4 substrates and inhibitors and/or CYP3A4 inducers with the appropriate washout period prior to the start of RO5045337 therapy. If the discontinuation of CYP3A4 substrates and inhibitors and/or CYP3A4 inducers is not medically feasible and no suitable substitutes are available, extreme caution should be taken with continued use of these meds during the study.
8) Patients who must stay on treatment with drugs known to prolong QT interval [Appendix 5] and/or may have a proarrhythmic effect, unless deemed necessary for the patient's safety by the PI.
9) Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia (corrected for serum albumin level), hypomagnesemia, and hypermagnesemia of Grade >= 2, as per NCI-CTCAE, version 3.0.
10) Patients with uncontrollable intercurrent illness including, but not limited to: symptomatic neurologic illness; active, uncontrolled, systematic (including opportunistic), life-threatening, or clinically significant infection at the time of planned study drug treatment; uncomtrolled pulmonary disease or hypoxia; or psychiatric illness that would limit compliance with study requirements, as per investigator's discretion.
11) Pregnant or breastfeeding patients.
12) Patients with reproductive potential not willing to use effective method of contraception.
13) HIV-positive patients receiving combination anti-retroviral therapy. |