Myelogenous Leukemia, Acute
Conditions
Brief summary
This multi-center, open-label, Phase 1b study will evaluate the safety, pharmacokinetics and efficacy of RO5045337 in combination with cytarabine in patients with acute myelogenous leukemia. In Arm A, cohorts of previously untreated patients deemed unsuitable for standard induction therapy will receive escalating oral doses of RO5045377 and cytarabine 20 mg/m2 subcutaneously daily for Days 1 to 10 of each 28-day cycle. In Arm B, cohorts of patients who have relapsed or are refractory after at least one cytarabine/anthracycline containing regimen will receive escalating oral doses of RO5045377 on Days 1 to 5 and cytarabine 1 gm/m2 intravenously on Days 1 to 6 of each 28-day cycle. Patients will receive up to 4 cycles of therapy, patients in Arm A who achieve hematologic response may continue additional cycles until disease progression.
Interventions
DRUGRO5045377
Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle
DRUGcytarabine
20 mg/m2 sc, Days 1 to 10 of each 28-day cycle
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
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 * Patients with histologically or cytologically documented acute myelogenous leukemia appropriate for cytarabine therapy including: * Arm A: Patients who have not received prior standard induction chemotherapy, considered unsuitable for standard induction therapy * Arm B: Patients who have failed their 1st or greater line of standard induction chemotherapy (primary refractory) or patients who originally achieved a complete response but are currently in first or greater relapse * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to NCI-CTC AE Grade \</=2 * Adequate hepatic and renal function * Patient must be willing to submit the blood sampling and bone marrow sampling for PK and PD analyses and exploratory biomarkers
Exclusion criteria
* History of allergic or toxic reactions attributed to cytarabine or a history of allergic reactions to components of the formulated product * Current evidence of CNS leukemia * Any severe and/or uncontrolled medical condition or other conditions that could affect the participation in the study * Pregnant or breastfeeding women * HIV-positive patients receiving combination anti-retroviral therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose/dose-limiting toxicities | approximately 12 months |
| Safety: Incidence of adverse events | approximately 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: Hematologic response | approximately 1 year |
| Pharmacodynamics: Biomarkers (MIC-1, protein, nucleic acid, other) from bone marrow/buccal tissue/blood | Pre-dose (and up to 12 hours post-dose Day 1 and Day 10 or Day 5) |
| Pharmacokinetics: Cmax/area under the concentration-time curve | Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5 |
Countries
Canada, France, Italy, United Kingdom, United States
Outcome results
None listed