• Efficacy [ Designated as safety issue: No ]
  
• Safety [ Designated as safety issue: Yes ]
  

• Predictors of response [ Designated as safety issue: No ]
  
• Cellular and molecular targets [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the efficacy of imatinib mesylate, in terms of reducing peripheral blood monocytosis or leukocytosis, in patients with chronic myelomonocytic leukemia or atypical chronic myeloid leukemia.
• Determine the safety of this drug in these patients.

Secondary

• Determine predictors of response in patients treated with this drug.
• Determine the cellular and molecular targets of this drug in these patients.

OUTLINE: This is a non-randomized, open-label, pilot study. Patients are stratified according to diagnosis (chronic myelomonocytic leukemia vs atypical chronic myeloid leuukemia).

Patients receive oral imatinib mesylate once daily for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients who respond to treatment are followed monthly for 12 months. Patients who do not respond to treatment are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 28-50 patients (14-25 per stratum) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

  • Chronic myelomonocytic leukemia (CMML) meeting the following criteria:

    • Persistent peripheral blood monocyte count > 1,000/mm^3
    • No Philadelphia chromosome or bcr/abl fusion gene
    • Less than 20% blasts in the blood and bone marrow
    • Dysplasia in one or more myeloid lineages* NOTE: *In the absence of dysplasia, CMML can be diagnosed if a cytogenetic abnormality is present in the marrow cells OR if monocytosis is persistent for at least 3 months (and all other causes of monocytosis have been excluded)

  • Atypical chronic myeloid leukemia meeting the following criteria:

    • Peripheral blood leukocytosis, including increased mature and immature neutrophils
    • Prominent dysgranulopoiesis
    • No Philadelphia chromosome or bcr/abl fusion gene
    • Neutrophil precursors ≥ 10% of WBC
    • Basophils < 2% of WBC
    • Monocytes < 10% of WBC
    • Hypercellular bone marrow with granulocytic proliferation and dysplasia
    • Less than 20% blasts in the blood and bone marrow

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 10,000/mm^3 (50,000/mm^3 with clinical evidence of bleeding)

Hepatic

• Transaminases ≤ 5 times upper limit of normal (ULN)
• Bilirubin ≤ 3 times ULN
• No severe hepatic disease that would limit life expectancy

Renal

• Creatinine < 2 mg/dL
• No severe renal disease that would limit life expectancy

Cardiovascular

• No severe cardiac disease that would limit life expectancy

Immunologic

• No uncontrolled infection
• No recent exposure to chicken pox
• No recent Herpes zoster (shingles) reactivation
• No known immunodeficiency
• HIV negative

Other

• No moribund status
• No severe metabolic disease that would limit life expectancy
• No other non-hematologic malignancy treated with chemotherapy within the past 5 years
• No chronic medical condition that would preclude study participation
• No psychiatric, affective, or other disorder that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior hematopoietic growth factors allowed

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 4 weeks since prior investigational therapy
• No concurrent alcohol consumption
• No concurrent grapefruit, grapefruit juice, or grapefruit-containing food or vitamins
• No other concurrent therapy