RATIONALE: BAY 43-9006 may stop the growth of cancer cells by blocking the enzymes necessary
for their growth.
PURPOSE: This phase II trial is studying how well BAY 43-9006 works in treating patients
with imatinib mesylate-resistant chronic phase chronic myelogenous leukemia.
- Determine the major hematologic response rate (complete and partial response) in
patients with imatinib mesylate-resistant chronic phase chronic myelogenous leukemia.
- Determine the safety of this drug in these patients.
- Determine the cytogenetic response rate in patients treated with this drug.
- Determine the duration of hematologic response in patients treated with this drug.
- Determine the duration of cytogenetic response in patients treated with this drug.
- Determine time to progression in patients treated with this drug.
- Determine overall survival of patients treated with this drug.
- Determined the molecular response in patients treated with this drug.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral BAY 43-9006 twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study.
- Diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in chronic
- 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
- 18 and over
- ECOG 0-2
- At least 16 weeks
- See Disease Characteristics
- WBC > 20,000/mm^3
- 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
- Creatinine ≤ 1.5 times ULN
- 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
- 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
- No substance abuse or medical, psychological, or social condition that would preclude
- No other concurrent severe disease or comorbidity that would preclude study
- No other unstable condition that would preclude study participation
PRIOR CONCURRENT 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
- 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
- Not specified
- Not specified
- No prior solid organ allograft
- More than 4 weeks since prior significant surgery
- 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