A Phase II Study of Gleevec in Ph+ Chronic Phase 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