OBJECTIVES:

• Determine the maximum tolerated dose of high-dose cytarabine when combined with imatinib mesylate in patients with blastic phase chronic myelogenous leukemia.
• Determine the safety of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the frequency of hematologic and cytogenetic responses, duration of response, and survival of patients treated with this regimen.

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

• Phase I: Patients who have not previously received imatinib mesylate receive oral imatinib mesylate daily on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive cytarabine IV over 2 hours every 12 hours on days 29-32. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity.
• Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients experience dose-limiting toxicity.
• Phase II: Additional patients are treated at the dose level preceding the MTD. Patients are followed monthly.

PROJECTED ACCRUAL: A maximum of 46 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia in myeloid blast crisis

  • At least 30% blasts in bone marrow
• Philadelphia chromosome positive by cytogenetic analysis OR
• bcr/abl translocation by fluorescent in situ hybridization
• Ineligible for or refused allogeneic stem cell transplantation
• Not previously treated with imatinib mesylate OR currently receiving imatinib mesylate with stable disease on 2 bone marrow biopsies at least 2 weeks apart

PATIENT CHARACTERISTICS:

Age:

• Phase I:

  • 18 to under 60

• Phase II:

  • 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin less than 3 times upper limit of normal (ULN)
• AST and ALT less than 3 times ULN

Renal:

• Creatinine less than 2 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and at least 3 months after study for male patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior allogeneic bone marrow or peripheral blood stem cell transplantation
• At least 48 hours since prior interferon alfa

Chemotherapy:

• At least 24 hours since prior hydroxyurea
• At least 6 weeks since prior busulfan
• No other prior chemotherapy for blast crisis (except hydroxyurea)
• Concurrent hydroxyurea or anagrelide for severe leukocytosis or thrombocytosis allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 4 weeks since prior investigational agents