• Complete and major cytogenetic response at 6 and 12 months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  
• Minor cytogenetic response at 6 and 12 months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  
• Complete hematologic response at 6 and 12 months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  
• Molecular response in patients with complete cytogenetic response at 6 and 12 months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  
• Treatment-related toxicity (i.e., grade 3 or 4 nonhematologic toxicity) as measured by NCI CTCAE v3.0 (Phase I) [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
  

Biological: recombinant interferon alfa
IFN-α will be given at a dose ranging up to 5 MIU daily via subcutaneous injection.
Drug: imatinib mesylate
Once daily oral administration of STI571 (imatinib mesylate) at a dose of 400 mg or 600mg for 12 months.
Other Name: STI571

OBJECTIVES:

• Determine the maximum tolerated dose of interferon alfa administered with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)
• Determine the safety and tolerability of this regimen in this patient population.
• Determine the complete, major, and minor cytogenetic response rates and complete hematologic response rate in patients after 6 and 12 months of treatment with this regimen.
• Determine the molecular response (reverse transcriptase-polymerase chain reaction for bcr-abl) rate in patients who have a complete cytogenetic response after 6 and 12 months of treatment with this regimen.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

• Phase I (closed to accrual as of 7/9/03): Patients receive oral imatinib mesylate once daily beginning on day 1 and interferon alfa (IFN-A) subcutaneously once daily or 3 times weekly beginning on day 14. Courses repeat every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of 1 year of therapy, patients may receive additional therapy, provided that the patient is benefiting from imatinib mesylate. IFN-A is discontinued in patients who achieve a molecular remission that is confirmed on 2 successive bone marrow samples. Imatinib mesylate is discontinued in patients who achieve and maintain a molecular remission for 2 years.

Sequential dose escalation of IFN-A is followed by sequential dose escalation of imatinib mesylate. Cohorts of 3-6 patients receive escalating doses of IFN-A and then imatinib mesylate until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for the phase I portion of this study. (Phase I closed to accrual as of 7/9/03.) A total of 40 patients will be accrued for the phase II portion of the study within 3-4 months.