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)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in chronic
phase

- Documented hematologic resistance to imatinib mesylate after a prior hematologic
response to imatinib mesylate administered at doses of at least 400 mg/day for at
least 3 months

- Documentation of resistance requires at least 2 measurements of WBC >
20,000/mm^3 within 2 weeks

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 16 weeks

Hematopoietic

- See Disease Characteristics

- WBC > 20,000/mm^3

Hepatic

- Bilirubin ≤ 2.0 times upper limit of normal (ULN)

- ALT and AST ≤ 3 times ULN

- PT (or INR) and PTT < 1.5 times ULN

- No chronic hepatitis B or C

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No New York Heart Association class III or IV congestive heart failure

- No cardiac arrhythmia requiring antiarrhythmics (excluding beta blockers or digoxin)

- No active coronary artery disease or ischemia

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- HIV negative

- No active clinically serious infection

- No known or suspected allergy to study drugs

- No other malignancy within the past 3 years except carcinoma in situ of the cervix,
adequately treated basal cell skin cancer, or superficial bladder tumors (Ta, Tis, or
T1)

- No substance abuse or medical, psychological, or social condition that would preclude
study participation

- No other concurrent severe disease or comorbidity that would preclude study
participation

- No other unstable condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 2 weeks since prior interferon

- More than 4 weeks since prior anticancer immunotherapy and recovered

- No prior allogeneic bone marrow or peripheral blood stem cell transplantation

- No concurrent bone marrow transplantation or stem cell rescue

Chemotherapy

- More than 2 days since prior hydroxyurea

- More than 2 weeks since prior cytarabine at a dose < 100 mg

- More than 4 weeks since prior cytarabine at a dose > 100 mg

- More than 4 weeks since other prior anticancer chemotherapy (6 weeks for
nitrosoureas, mitomycin, or busulfan) and recovered

- No concurrent chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- No prior solid organ allograft

- More than 4 weeks since prior significant surgery

Other

- More than 2 days since prior imatinib mesylate

- More than 4 weeks since prior investigational drugs

- Concurrent therapeutic anticoagulation (e.g., warfarin or heparin) allowed as long as
no underlying abnormality exists

- No concurrent antiepileptic drugs for seizure disorders

- No concurrent ketoconazole, itraconazole, or ritonavir

- No concurrent products containing grapefruit juice

- No other concurrent anticancer therapy

- No other concurrent investigational drugs