RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining STI571 and chemotherapy in treating patients who have chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
relapsing chronic myelogenous leukemia blastic phase chronic myelogenous leukemia Philadelphia chromosome positive chronic myelogenous leukemia	Drug: cytarabine  Drug: imatinib mesylate  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States; Recruiting
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States; Recruiting
Oregon
      Oregon Cancer Institute, Portland,  Oregon,  97239,  United States; Recruiting
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Ronald Paquette, MD,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068441; UCLA-0011009; UCLA-NCI-1870; NCI-1870
Record last reviewed:  December 2001
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00015834
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08