• To evaluate the durations of PCR negativity, cytogenetic response, hematologic control, and survival. [ Time Frame: November 2012 ] [ Designated as safety issue: No ]
  

• To analyze differences in response rates and in prognosis within different risk groups and patient characteristics. [ Time Frame: November 2012 ] [ Designated as safety issue: No ]
  

Imatinib mesylate is a drug that blocks a protein that is responsible for the development of CML. PEG-Intron is a natural substance made by the cells of the immune system and helps to control CML. GM-CSF is a hormone that helps to stimulate the production of white blood cells.

Before treatment starts, you will have a physical exam, blood tests (around 1-2 tablespoons), and a sample of bone marrow collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

During the study you will take 4 tablets of imatinib mesylate by mouth 2 times a day (8 tablets a day total). Imatinib mesylate should be taken each morning and evening with a large glass of water. Bottles containing the tablets will be given to you every month. You will also be given a "pill diary" to write down when (day and time) you take the drug. You will also write in the diary any side effects you may experience. You should bring the diary, any unused tablets, and empty bottles of imatinib mesylate with you to every visit to the study doctor. Any unused supplies must be returned at the end of the study.

After completing 6 months of imatinib mesylate therapy, you will be randomly assigned (as in the toss of a coin) to one of two groups. Patients in the first group will be given PEG-Intron and GM-CSF in addition to imatinib mesylate therapy. Patients in the other group will continue taking only imatinib mesylate.

If you are assigned to the group that will receive PEG-Intron and GM-CSF, you will continue taking imatinib mesylate. In addition, PEG-Intron will be given as an injection under the skin once a week. Sargramostim will be given as an injection under the skin 3 times a week. You and/or your family members can be taught to give these injections.

Every 1-2 weeks during the first 4 weeks of the study, you will have around 2 teaspoons of blood drawn for routine blood tests and to measure the amount of imatinib in your blood. The blood tests will then be repeated every 6 to 8 weeks (or more often if your doctor feels it is necessary) for as long as you are on the study. A bone marrow sample will also be taken every 3 months for the first year and then every 4 to 6 months for as long as you are on the study to check on the status of the disease .

You will be asked to visit the doctor for a physical exam and to have vital signs measured. These visits will be scheduled at least every 3 months while you are on the study. The visits may be scheduled more often depending on the status of the disease.

Treatment in both groups may be continued for up to 7-10 years, or as long as the doctor feels is necessary to control the leukemia.

If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. However, their use in this study is investigational. A total of 98 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

• Patients with Ph-positive CML in early chronic phase CML who have received no or minimal prior therapy, (<1 month of prior IFN-alpha (with or without ara-C) and/or Gleevec).
• ECOG performance of 0-2.
• Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGPT < 2.5 x ULN, creatinine < 1.5 x ULN
• Signed informed consent.

Exclusion Criteria:

• NYHA cardiac class 3-4 heart disease.
• Psychiatric disability (psychosis)
• Pregnant or lactating females
• Late chronic phase, accelerated or blastic phase

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
   • 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 signs of accelerated phase are present, and analyzed separately.