• Response rate [ Designated as safety issue: No ]
• Frequency of adverse events [ Designated as safety issue: Yes ]
• Toxicity [ Designated as safety issue: Yes ]

• Response rate
• Frequency of adverse events
• Toxicity

• Progression-free survival [ Designated as safety issue: No ]
• Effects of imatinib mesylate on biological markers [ Designated as safety issue: No ]
• Cytogenetic response [ Designated as safety issue: No ]

• Progression-free survival
• Effects of imatinib mesylate on biological markers
• Cytogenetic response

RATIONALE: Imatinib mesylate may stop the growth of myelofibrosis by blocking certain enzymes necessary for cell growth.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have myelofibrosis.

OBJECTIVES:

• Determine the complete and partial response rate in patients with myelofibrosis treated with imatinib mesylate.
• Determine the safety of this drug in these patients.
• Determine the effects of this drug on the bone marrow morphology, including effects on bone marrow fibrosis, osteosclerosis, and cellularity, in these patients.
• Assess the effects of this drug on surrogate biologic endpoints, including platelet-derived growth factor (PDGFR) expression by immunohistochemistry, PDGFR signaling, and circulating progenitor (CD34 positive) cells, in these patients.
• Determine the effects of this drug on bone marrow cytogenetics in patients with an abnormal karyotype.

OUTLINE: This is a multicenter study. Patients are stratified according to Dupriez risk score (low vs intermediate vs high).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 3-17.5 months.

• Chronic Myeloproliferative Disorders
• Leukemia

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Histologically confirmed myeloid metaplasia with myelofibrosis (MMM)

    • All subtypes eligible

      • Chronic idiopathic myelofibrosis
      • Agnogenic myeloid metaplasia
      • Post-thrombocythemic or post-polycythemic myelofibrosis
    • Must meet the standard Italian Diagnostic Criteria for MMM OR

• Histologically confirmed chronic myelomonocytic leukemia (CMMOL) with t(5;12)(q31;p12) or TEL-platelet-derived growth factor (PDGFR)-beta rearrangement

  • Patients with CMMOL and the t(5;7)(q33;q11.2) or other chromosomal translocations resulting in activation of PDGFR are also eligible
  • Must meet the standard World Health Organization Diagnostic Criteria for CMMOL

• Meets criteria for 1 of the following:

  • Anemia (hemoglobin less than 11 g/dL)
  • Splenomegaly by palpation and ultrasound
• Philadelphia chromosome or bcr-abl rearrangement negative

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST/ALT less than 2.5 times ULN (unless due to liver involvement with disease)

Renal:

• Creatinine less than 2 times ULN

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for up to 3 months after study participation
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to imatinib mesylate
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situations that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior epoetin alfa or filgrastim (G-CSF)
• No concurrent biologic agents

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior androgenic steroids
• No concurrent androgenic steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy, including splenic irradiation
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 4 weeks since other prior therapy
• Any number of prior treatment regimens allowed
• No other concurrent investigational or commercial anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent therapeutic anticoagulation with warfarin
• Concurrent therapeutic anticoagulation with low-molecular weight heparin (e.g., enoxaparin) or unfractionated heparin allowed