This study will determine the maximum tolerated dose of RO5045337 and the optimal associated 4 weekly dosing schedule of RO5045337, administered as monotherapy in patients with hematologic neoplasms. A first cohort of patients will receive the starting dose of 20mg/m2/day orally, once daily for 10 days in each 28 day cycle. Subsequent cohorts of patients will receive dose escalations, and possible changes in dosing schedule, based on tolerability and pharmacokinetic knowledge gained from prior treatment cohorts. Different formulations of RO5045337 will be tested and the food effect evaluated. The anticipated time on study treatment is until disease progression or intolerable toxicity.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
116
Multiple ascending doses
Unnamed facility
Duarte, California, United States
Unnamed facility
New Brunswick, New Jersey, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Houston, Texas, United States
Unnamed facility
Toronto, Ontario, Canada
Unnamed facility
Montreal, Quebec, Canada
Unnamed facility
Bologna, Emilia-Romagna, Italy
Unnamed facility
Rome, Lazio, Italy
Unnamed facility
Glasgow, United Kingdom
Unnamed facility
Leeds, United Kingdom
...and 1 more locations
Maximum tolerated dose/Dose-limiting toxicities
Time frame: approximately 4.5 years
Safety: Incidence of adverse events
Time frame: approximately 4.5 years
Comparison of daily versus twice daily dosing: Incidence of adverse events
Time frame: approximately 4.5 years
Pharmacokinetics: Blood/Urine concentrations
Time frame: Pre- and post-dose multiple sampling Days 1+2/Days 1+10 Cycle 1, post-dose sampling Days 11+15 Cycle 1, pre-dose Days 1+2 Cycle 2
Pharmacodynamics: Blood leukemia cells/MIC-1 protein level/CD33+CD34 markers
Time frame: Pre- and post-dose Days 1+10 Cycle 1, pre-dose Day 2 Cycle 1, Days 1+2 Cycle 2
Clinical response: Clinical/hematologic malignancy assessments
Time frame: approximately 4.5 years
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