Clinical trial NCT01635296: A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia
Official title: A Multicenter, Open Label, Phase 1B Study of Escalating Doses of RO5045337 Administered Orally, With Cytarabine Administered A) Subcutaneously, or B) Intravenously, in Patients With Acute Myelogenous Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelogenous Leukemia, Acute
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-07-09
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose/dose-limiting toxicities
timeFrame: approximately 12 months
measure: Safety: Incidence of adverse events
timeFrame: approximately 12 months
Secondary outcomes:
measure: Efficacy: Hematologic response
timeFrame: approximately 1 year
measure: Pharmacodynamics: Biomarkers (MIC-1, protein, nucleic acid, other) from bone marrow/buccal tissue/blood
timeFrame: Pre-dose (and up to 12 hours post-dose Day 1 and Day 10 or Day 5)
measure: Pharmacokinetics: Cmax/area under the concentration-time curve
timeFrame: Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5
Other outcomes:
Locations:
city: Valhalla
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: San Antonio
country: United States
state: Texas
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Marseille
country: France
city: Bologna
country: Italy
state: Emilia-Romagna
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: