RATIONALE: BAY 43-9006 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of BAY 43-9006 in treating patients who have imatinib mesylate-resistant chronic phase chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
chronic phase chronic myelogenous leukemia Philadelphia chromosome positive chronic myelogenous leukemia relapsing chronic myelogenous leukemia	Drug: sorafenib  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• 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.

Secondary

• 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.

Tertiary

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States

Study chairs or principal investigators

Ronald Paquette, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000367117; UCLA-0312018-01; BAYER-10941; NCT00085007
Record last reviewed:  February 2005
Last Updated:  February 24, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085007
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08