Back to resultsA Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia
Primary Purpose
Myelogenous Leukemia, Acute
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO5045377
RO5045377
cytarabine
cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Myelogenous Leukemia, Acute
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
A: Previously untreated
B: Relapse/Refractory
Arm Description
Outcomes
Primary Outcome Measures
Maximum tolerated dose/dose-limiting toxicities
Safety: Incidence of adverse events
Secondary Outcome Measures
Efficacy: Hematologic response
Pharmacodynamics: Biomarkers (MIC-1, protein, nucleic acid, other) from bone marrow/buccal tissue/blood
Pharmacokinetics: Cmax/area under the concentration-time curve
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01635296
Brief Title
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
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelogenous Leukemia, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A: Previously untreated
Arm Type
Experimental
Arm Title
B: Relapse/Refractory
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RO5045377
Intervention Description
Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
RO5045377
Intervention Description
Multiple escalating oral doses, Days 1 to 5 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
20 mg/m2 sc, Days 1 to 10 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
1 gm/m2 iv, Days 1 to 6 of each 28-day cycle
Primary Outcome Measure Information:
Title
Maximum tolerated dose/dose-limiting toxicities
Time Frame
approximately 12 months
Title
Safety: Incidence of adverse events
Time Frame
approximately 12 months
Secondary Outcome Measure Information:
Title
Efficacy: Hematologic response
Time Frame
approximately 1 year
Title
Pharmacodynamics: Biomarkers (MIC-1, protein, nucleic acid, other) from bone marrow/buccal tissue/blood
Time Frame
Pre-dose (and up to 12 hours post-dose Day 1 and Day 10 or Day 5)
Title
Pharmacokinetics: Cmax/area under the concentration-time curve
Time Frame
Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
City
Marseille
ZIP/Postal Code
13273
Country
France
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M204BX
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia
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