• Response rate [ Designated as safety issue: No ]
• Disease-free survival [ Designated as safety issue: No ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Toxic effects [ Designated as safety issue: Yes ]

• Response rate
• Disease-free survival
• Pharmacokinetics
• Toxic effects

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

PURPOSE: This phase II trial is studying imatinib mesylate to see how well it works in treating patients with chronic myelogenous leukemia.

OBJECTIVES:

• Determine the response rate in patients with Philadelphia chromosome positive chronic phase chronic myelogenous leukemia treated with imatinib mesylate.
• Determine the disease-free survival of patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the toxic effects of this drug in these patients.
• Determine the rates of hematological, cytogenetic, and molecular response and time to response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease (chronic myelogenous leukemia [CML] in first chronic phase after failing interferon therapy or demonstrating intolerance to interferon [closed to accrual as of 12/05/03] vs CML relapsing after stem cell transplantation or in second or subsequent chronic phase [closed to accrual as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior treatment [closed to accrual as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior treatment).

Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve a complete hematologic response after 3 courses or a partial or complete cytogenic response after 6 courses are removed from the study.

PROJECTED ACCRUAL: A total of 109 patients (30 for stratum I [closed to accrual as of 12/05/03] and stratum II [closed to accrual as of 7/29/05], 34 for stratum III [closed to accrual as of 7/29/05], and 45 for stratum IV) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of Philadelphia chromosome positive (Ph+) chronic phase chronic myelogenous leukemia (CML)

• Stratum I (closed to accrual as of 12/05/03):

  • CML in first chronic phase with resistance to interferon alfa (IFN-A) therapy defined as one of the following:

    • WBC count at least 20,000/mm^3 after at least 3 months of treatment with an IFN-A-containing regimen
    • Rising WBC count (at least 100% increase to a level of at least 20,000/mm^3) by two samples at least two weeks apart while receiving treatment with an IFN-A-containing regimen
    • At least 66% Ph+ cells in bone marrow after 1 year of IFN-A therapy
    • At least 30% increase in Ph+ cells in bone marrow after IFN-A-induced cytogenetic response while continuing to receive IFN-A therapy OR
  • Intolerance to interferon therapy defined as more than two grade 2 toxic effects or any grade 3 toxic effect related to interferon therapy, except grade 3 fever, that is persistent beyond the first 28-day course of therapy and unresponsive to standard supportive care interventions

• Stratum II (closed to accrual as of 7/29/05): CML recurring after stem cell transplantation or in second or subsequent chronic phase

  • No molecular relapse (only evidence is detection of bcr-abl rearrangement with normal bone marrow and blood morphology and normal standard cytogenetic analysis)
• Stratum III (closed to accrual as of 7/29/05): Newly diagnosed CML in first chronic phase with no prior treatment except hydroxyurea
• Stratum IV: Newly diagnosed CML in first chronic phase with no prior treatment except hydroxyurea

• No accelerated or blast phase defined as one or more of the following:

  • WBC doubling time less than 5 days
  • Chloroma
  • Medullary fibrosis
  • More than 10% blasts in peripheral blood or bone marrow
  • More than 20% promyelocytes in peripheral blood or bone marrow
  • More than 20% basophils and eosinophils in peripheral blood

PATIENT CHARACTERISTICS:

Age:

• Under 22

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• See Disease Characteristics
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram

Hepatic:

• Bilirubin no greater than 1.5 times normal
• ALT less than 3.0 times normal
• Albumin greater than 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No CNS toxicity greater than grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior immunotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
• At least 3 months since prior stem cell transplantation (SCT) (patients with allogeneic SCT must have no active graft-versus-host disease [GVHD] and have stable use of steroids) (for patients in stratum II only )
• At least 1 week since prior growth factors
• At least 1 week since prior biologic therapy, including interferon alfa (for patients in stratum I [closed to accrual as of 12/05/03] and stratum II only)
• Recovered from prior immunotherapy
• No concurrent immunomodulating agents

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
• At least 6 weeks since prior busulfan or nitrosoureas
• At least 7 days since prior hydroxyurea
• At least 7 days since prior low-dose cytarabine (less than 30 mg/m^2 every 12 to 24 hours)
• At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5 to 7 days)
• At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12 to 24 hours for 6 to 12 doses)
• At least 21 days since all other cytotoxic chemotherapy
• Recovered from prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent steroids other than for controlled GVHD in patients with prior allogeneic SCT

Radiotherapy:

• No prior radiotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
• At least 2 weeks since prior local palliative (small port) radiotherapy*
• At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of pelvis*
• At least 6 weeks since prior substantial bone marrow radiotherapy*
• Recovered from prior radiotherapy NOTE: * For patients in stratum I (closed to accrual as of 12/05/03) and stratum II only

Surgery:

• Not specified

Other:

• No prior imatinib mesylate
• No concurrent enzyme-activating anticonvulsants
• No concurrent warfarin
• No concurrent naturopathic agents or herbal medicines
• No other concurrent investigational agents
• Concurrent low-molecular weight heparin allowed