Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

Inclusion Criteria:

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
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
Performance status - ECOG 0-2
At least 8 weeks
See Disease Characteristics
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
Bilirubin no greater than 1.5 times normal
ALT less than 3.0 times normal
Albumin greater than 2 g/dL
Creatinine no greater than 1.5 times normal
Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled infection
No CNS toxicity greater than grade 2
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
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
No concurrent steroids other than for controlled GVHD in patients with prior allogeneic SCT
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
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