Myelogenous Leukemia, Acute
Conditions
Brief summary
This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of RO5429083 alone and in combination with cytarabine in patients with acute myelogenous leukemia. In Part A, patients will receive multiple escalating doses of RO5429083 intravenously. In Part B, patients will receive RO5429083 plus up to 4 cycles of cytarabine (1000 mg/m2 iv daily for 5 consecutive days). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Interventions
DRUGRO5429083
Multiple escalating doses
DRUGcytarabine
1000 mg/m2 iv daily for 5 consecutive days, up to 4 cycles
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 * Histologically or cytologically confirmed, acute myelogenous leukemia (all subtypes except acute promyelotic leukemia) according to WHO criteria * 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, except alopecia * Adequate hepatic and renal function * Patient must be willing to submit blood and bone marrow samples for PK and PD analyses and exploratory biomarkers
Exclusion criteria
* Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea * History of allergic reactions attributed to components of cytarabine and/or the formulated product * Current evidence of CNS leukemia * Increased QTc interval (QTc \> 470 ms), baseline resting bradycardia \< 45 beats per minute, or baseline resting tachycardia \< 100 beats per minute * Family history of long QT syndrome or other risk factors for torsades de pointes, and/or the use of concomitant medications that prolong QT/QTc interval * Uncontrollable intercurrent illness * Pregnant or breast-feeding women * HIV-positive patients receiving anti-retroviral therapy * Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose) | approximately 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Clinical response according to hematologic malignancy assessments | approximately 24 months |
| Pharmacokinetics o RO5429083 alone and in combination with cytarabine: Area under the concentration-time curve (AUC) | Pre-dose and up to 96 hrs post-dose |
| Pharmacokinetics of cytarabine in combination with RO5429083: Area under the concentration-time curve (AUC) | Pre-dose and up to 24 hrs post-dose, Cycles 1 and 3 |
| Pharmacodynamics: Biomarker levels in blood/bone marrow | Pre-dose and up to 96 hrs post-dose |
Countries
France, Germany, Italy
Outcome results
None listed