A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

Phase 1

Completed

• Conditions: Myelogenous Leukemia, Acute
• Interventions: Drug: RO5045377; Drug: cytarabine

• Registration Number: NCT01635296
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-06-12
• Study Start: 2012-07
• Study First Submitted QC: 2012-07-04
• Study First Posted: 2012-07-09
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: Previously untreated	RO5045377	-
B: Relapse/Refractory	RO5045377	-
A: Previously untreated	cytarabine	-
B: Relapse/Refractory	cytarabine	-

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose/dose-limiting toxicities	approximately 12 months
Safety: Incidence of adverse events	approximately 12 months

Secondary Outcome Measures

Name	Time	Method
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