RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction.

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.
• Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.
• Determine the non-dose-limiting toxic effects of this drug in these patients.
• Determine the response rate of these patients treated with this drug.
• Correlate the Childs-Pugh classification of hepatic dysfunction with observed toxic effects, pharmacodynamics, and pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to liver dysfunction (normal vs mild vs moderate vs severe).

Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

• Chronic Myeloproliferative Disorders
• Gastrointestinal Stromal Tumor
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases
• Precancerous/Nonmalignant Condition
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed surgically incurable solid tumor or hematologic malignancy for which no standard or palliative therapy exists or is no longer effective

  • All tumor types are eligible, including:

    • Chronic myelogenous leukemia or other Philadelphia chromosome-positive leukemia OR
    • Gastrointestinal stromal tumors
• Patients with gliomas that require corticosteroids or anticonvulsants must be on a stable dose and seizure-free for 1 month
• No unstable or untreated (non-irradiated) brain metastases

PATIENT CHARACTERISTICS:

Age:

• Over 15 (Patients 15 -18 years are eligible only if refractory disease and no alternative therapy options exist)

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No active hemolysis

Hepatic:

• See Surgery
• No evidence of biliary sepsis

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Able to swallow pills
• No other uncontrolled concurrent illness that would preclude study participation
• No ongoing or active infection
• No uncontrolled diarrhea
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 6 months after study completion

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 24 hours since prior colony-stimulating factors
• No concurrent colony-stimulating factors

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics
• At least 10 days since prior placement of shunt for treatment of biliary obstruction
• At least 14 days since prior major surgery
• No prior solid organ transplantation

Other:

• No other concurrent investigational agents
• No concurrent therapeutic doses of warfarin for anticoagulation
• No other concurrent investigational or commercial agents or therapies for treatment of this disease
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent acetaminophen of more than 4,000 mg/day