OBJECTIVES:

• Determine the maximum tolerated dose of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction.
• Determine the effects of renal dysfunction on the plasma pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the safety of this drug in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to creatinine clearance (at least 60 mL/min vs 40-59 mL/min vs 20-39 mL/min vs less than 20 mL/min vs any creatinine clearance and undergoing dialysis).

Patients receive oral imatinib mesylate once or twice daily on days 1 and 4-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in each 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 60-69 patients (about 12 per stratum) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which no standard curative therapy exists or palliative measures are no longer effective

  • Hematological malignancies

    • Philadelphia chromosome-positive patients should be enrolled on another NCI or Novartis trial, if possible
  • Myeloproliferative disorders

  • Any solid tumor, and especially:

    • Gastrointestinal stromal tumors
    • Gliomas
• No untreated (unirradiated) or unstable brain metastases

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,000/mm^3 OR
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 1.5 times upper limit of normal

Renal:

• Abnormal kidney function allowed

Cardiovascular:

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

Other:

• No seizures within the past month (for patients with glioma)
• No other concurrent uncontrolled illness that would preclude study entry
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study consent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy allowed
• No concurrent colony-stimulating factor therapy

Chemotherapy:

• More than 24 hours since prior hydroxyurea to maintain WBC count in leukemia patients
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

• Prior hormonal therapy allowed
• Concurrent corticosteroids must be at a stable dose
• No concurrent oral contraceptives

Radiotherapy:

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

Surgery:

• No prior liver, kidney, or lung transplantation
• At least 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)

Other:

• Prior imatinib mesylate allowed
• No other concurrent investigational agents
• No concurrent therapeutic doses of warfarin
• No concurrent tacrolimus or cyclosporine as an immunosuppressive agent
• No concurrent herbal supplements, vitamins, or other nontraditional compounds
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent acetaminophen of more than 4,000 mg total daily dose
• Concurrent anticonvulsants must be at a stable dose
• Concurrent renal dialysis allowed