Hematologic Neoplasms
Conditions
Brief summary
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.
Interventions
DRUGRO5045337
Multiple ascending doses
Sponsors
Hoffmann-La Roche
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>=18 years of age * Acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia in blast phase, refractory chronic lymphocytic leukemia/small cell lymphocytic lymphoma * Relapsed or refractory to approved therapies, or no viable alternative therapy available * ECOG performance status of 0-2
Exclusion criteria
* Patients receiving any other agent or therapy to treat their malignancy * Pre-existing gastrointestinal disorders which may interfere with absorption of drugs * Clinically significant cardiovascular disease * Pregnant or lactating women * HIV-positive patients receiving combination antiretroviral therapy * Amendment J and onward for patients in the food effect evaluation and for all subsequent patients if dosing with a high fat/high calorie meal is found to be optimal: Patients with allergies to any ingredient in the defined liquid supplement and/or inability to tolerate a high fat/high calorie meal twice daily on scheduled RO5045337 dosing days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose/Dose-limiting toxicities | approximately 4.5 years |
| Safety: Incidence of adverse events | approximately 4.5 years |
| Comparison of daily versus twice daily dosing: Incidence of adverse events | approximately 4.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Blood/Urine concentrations | 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 | 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 | approximately 4.5 years |
Countries
Canada, Italy, United Kingdom, United States
Outcome results
None listed