Open Label Phase II Study of BAY 43-9006 in Chronic Myelogenous Leukemia (CML) Patients Resistant to Gleevec (ORACLE)

Open Label Multi-Centric Phase II Study of the Raf Kinase Inhibitor BAY 43-9006 in Chronic Myelogenous Leukemia (CML) Patients Resistant to Gleevec (Imatinib)

The purpose of this study is to evaluate the anti-cancer activity and safety of Bay 43-006, in patients who have Chronic Myelogenous Leukemia that resisted to Gleevec treatment, one of the standard medication administered for these patients.

Study Overview

• Status: Completed
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: Nexavar (Sorafenib, BAY43-9006)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon Cedex, France, 69437
  • Paris, France, 75010
  • Poitiers Cedex, France, 86021
• United States
  • Oregon
    • Portland, Oregon, United States, 97239

Participation Criteria

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:- Have Philadelphia chromosome positive chronic myelogenous leukemia (CML) in chronic phase, as per IBMTR criteria- Have documented hematologic resistance to Gleevec (Imatinib) following a prior hematologic response to Gleevec administered at doses of at least 400 mg/d for at least 3 months.- Have WBC >20 x 109/L at study entry- Have an ECOG performance status. Status of 0, 1 or 2- Have an anticipated survival of at least 16 weeks.- Be able to comply with study procedures and follow-up examinations.- Signed informed consent must be obtained prior to any study specific procedures. Exclusion Criteria:- Congestive heart failure > class II as defined by the New York Heart Association Functional Classification (NYHA)- Cardiac arrhythmias requiring antiarrythmics (excluding beta blockers or digoxin)- Active coronary artery disease or ischemia- History of HIV infection or chronic hepatitis B or C - Active clinically serious infections (> grade 2 NCI-CTC)- Patients with seizure disorder requiring anti-epileptic drugs- History of solid organ allograft

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Nexavar (Sorafenib, BAY43-9006); Patients will receive Bay 43-9006 400 mg po twice daily in a continuous, uninterrupted schedule. Treatment will continue until there is objective evidence of disease progression, or until evidence of toxicities that are unacceptable and thought to be related to study drug, which requires discontinuation of drug, or due to withdrawn patient consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the major hematologic response rate (i.e. complete and partial hematologic responses) associated with BAY 43-9006 in patients with chronic phase CML resistant to Gleevec.	Every 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the cytogenetic response rate associated with BAY 43-9006.	Every 3 months
To evaluate the duration of hematologic response to BAY 43-9006.	Throughout study until end of response
To evaluate the duration of cytogenetic response to BAY 43-9006.	Throughout study until end of response
To assess time to progression.	Until event occurs
To assess overall survival..	During Follow up
To evaluate the molecular response and to perform the pharmacodynamic assessment by analysis the following biomarkers: phospho-Erk, Crkl, phospho-S6	At 2 months and at last visit
To assess the safety of BAY 43-9006 in patients with chronic phase CML resistant to Gleevec.	Ongoing

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: April 15, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimate): April 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 10941