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

November 1, 2016 updated by: Hoffmann-La Roche

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)

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
      • Marseille, France, 13273
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
      • Glasgow, United Kingdom, G12 0YN
      • Manchester, United Kingdom, M204BX
    • New York
      • Valhalla, New York, United States, 10595
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
    • Texas
      • San Antonio, Texas, United States, 78229

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: Previously untreated
Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle
Multiple escalating oral doses, Days 1 to 5 of each 28-day cycle
20 mg/m2 sc, Days 1 to 10 of each 28-day cycle
1 gm/m2 iv, Days 1 to 6 of each 28-day cycle
Experimental: B: Relapse/Refractory
Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle
Multiple escalating oral doses, Days 1 to 5 of each 28-day cycle
20 mg/m2 sc, Days 1 to 10 of each 28-day cycle
1 gm/m2 iv, Days 1 to 6 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose/dose-limiting toxicities
Time Frame: approximately 12 months
approximately 12 months
Safety: Incidence of adverse events
Time Frame: approximately 12 months
approximately 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy: Hematologic response
Time Frame: approximately 1 year
approximately 1 year
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)
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
Time Frame: Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5
Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

June 12, 2012

First Submitted That Met QC Criteria

July 4, 2012

First Posted (Estimate)

July 9, 2012

Study Record Updates

Last Update Posted (Estimate)

November 2, 2016

Last Update Submitted That Met QC Criteria

November 1, 2016

Last Verified

November 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelogenous Leukemia, Acute

3
Subscribe