The goal of this clinical research study is to see if imatinib mesylate (Gleevec, STI571) with or without IFNa and ara-C can improve CML in chronic phase.

The rationale behind the design is based on the following: 1. Gleevec has produced the best results ever in CML. In IFN-a failures, the CHR rate was above 90% and, after 6 months of therapy, the major cytogenetic response rate was 50% (complete 30%). Thus, given in newly diagnosed CML, the results should be at least as good if not better. 2. Gleevec after 6 months of therapy in IFN-a failure was associated with a complete cytogenetic response rate of 30%, versus only 3% at 6 months with IFN-a in newly diagnosed patients. Since the durable complete cytogenetic response rate with IFN-a at 10 years is 20% (off therapy in 15%), Gleevec may lead to long-term event-free survival (potential cure) in a significant proportion (perhaps 30% to 50%) of patients with minimal toxicity. 3. While the addition of IFN-a plus ara-C may increase that proportion, it is cumbersome (2 injections daily) and has significant side effects. Thus it is best to select out patients who respond well to Gleevec alone, and use the combination only in those with inadequate response to Gleevec. This, based on past experiences with IFN-a, will be defined as a) failure to achieve CHR after 3 or more months of therapy, or b) failure to achieve a major cytogenetic response after 12 months or more of therapy. 4. PCR quantitation is a useful indicator of response to therapy and of the need to continue, change or perhaps discontinue all therapies. The critical PCR ratio for long-term event-free survival is 0.045%.

The objectives are:(1) to increase the proportion of patients achieving a complete cytogenetic response in patients with Ph-positive early chronic phase CML using initial Gleevec therapy, and adding IFN-a + ara-C if the response to Gleevec is not satisfactory;(2) secondary end-points: to evaluate the duration of cytogenetic response, the duration of hematologic control, and survival;(3)to analyze differences in response rates and in prognosis within different risk groups and patient characteristics.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

INCLUSION:

• Patients age 15 years or older with a diagnosis of Ph-positive or Bcr-positive CML in early chronic phase CML (diagnosis < 12 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as less than 1 month of prior IFN-a or ara-C.
• ECOG performance of 0-2.
• Serum bilirubin less than 2mg%, serum creatinine less than 2mg%.

EXCLUSION:

• NYHA Class 3-4 heart disease
• Psychiatric disability (psychosis)
• Pregnant or lactating females
• Women of pregnancy potential must practice contraception.
• Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
• Patients in late chronic phase, accelerated phase or blastic phase are excluded.
• The definitions of CML phases are as follows:

a. Early chronic phase: time from diagnosis to therapy < 12 months Late chronic phase: time from diagnosis to therapy > 12 months

b. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow.

c. Accelerated phase CML: presence of any of the following features:

* Peripheral or marrow blasts 15% or more * Peripheral or marrow basophils 20% or more * Thrombocytopenia < 100 x 109/L unrelated to therapy * Documented extramedullary blastic disease outside liver or spleen due to past causes

d. Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome is part of accelerated phase CML. Ph chromosome variants or complex Ph chromosome translocations are not considered to indicate disease acceleration. We have recently found clonal evolution to have a variable prognostic impact and may be suppressed with IFN-a therapy. Hence these patients will be eligible if no other accelerated phase signs are present, and analyzed separately.

• Inclusion of women and minorities: As per NIH policy, women and members of minorities will be included in this protocol as they are referred in the CML population. Their distribution is similar to the general referral profiles for CML: about 50% of CML patients are females and 25% to 30% are members of minorities. There are no exclusions of women or minorities based on the study objectives.