The rationale behind the design is based on the following:

1. Gleevec is the most active agent so far against CML. In IFN- failures, Gleevec induces CHR in above 90% and major cytogenetic response in above 50% (complete, i.e. Ph 0%, in above 30%).
2. IFN- plus ara-C results in a CHR rate of 90%, and a cytogenetic response rate of 65% to 70% which is complete in 25%.

The objectives are:

Primary Objective: To increase the proportion of patients achieving a complete cytogenetic response in patients with Ph-positive early chronic phase CML using initial Gleevec therapy.

Secondary Objective: To evaluate the duration of cytogenic response, duration of hematologic response and survival.

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:

  1. Early chronic phase: time from diagnosis to therapy < 12 months Late chronic phase: time from diagnosis to therapy > 12 months
  2. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow.

  3. 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
  4. 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.