An Open Label Study to Investigate the Maximum Tolerated Dose of RO5045337 in Patients With Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) in Blast Phase, or Refractory Chronic Lymphocytic Leukemia/Small Cell Lymphocytic Lymphoma (CLL / SCLL)
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 116
- Primary Endpoint
- Maximum tolerated dose/Dose-limiting toxicities
Study Overview
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.
Study Design
- Study Type
- Interventional
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
1
Intervention: RO5045337 (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)