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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Chronic Myelogenous Leukemia

Intervention / Treatment
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* Drug: Nexavar (Sorafenib, BAY43-9006)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |