RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate and chemotherapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have newly diagnosed chronic myeloid leukemia.

Condition	Treatment or Intervention	Phase
chronic 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

OBJECTIVES:

• Determine the maximum tolerated dose of imatinib mesylate and cytarabine in patients with newly diagnosed chronic phase chronic myeloid leukemia.
• Determine the feasibility of this regimen as defined by dose-limiting toxicity of this regimen and treatment-related mortality in no more than 5% of these patients.
• Determine the rate and duration of molecular response, complete hematological response, and complete cytogenetic response in patients treated with this regimen.
• Determine the time to treatment failure of patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

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

Patients receive oral imatinib mesylate alone once daily on days 1-21. Patients then receive oral imatinib mesylate once daily and cytarabine IV over 1-3 hours on days 1-7. Combination therapy repeats every 28-42 days for 2 courses. Patients then receive maintenance oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 5-20 patients receive escalating doses of imatinib mesylate and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 5/5, 5/10, or 5/20 patients experience dose-limiting toxicity.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed chronic myeloid leukemia in first chronic phase (within the past 6 months)
• Philadelphia-chromosome positive OR
• bcr-abl rearrangement
• No prior treatment within the past 6 months other than hydroxyurea

PATIENT CHARACTERISTICS: Age:

• 18 to 65

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No hepatic dysfunction
• Bilirubin less than 2 times normal
• ALT less than 4 times normal

Renal:

• No renal dysfunction
• Creatinine less than 2.3 mg/dL

Cardiovascular:

• No severe cardiac dysfunction
• No New York Heart Association class II-IV heart disease

Pulmonary:

• No severe pulmonary disease

Other:

• HIV negative
• No severe neurologic disease
• No active uncontrolled infection
• No other active malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• No concurrent allogeneic transplantation with an HLA-A, B, DR-matched sibling donor or matched-unrelated donor

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Other:

• No concurrent grapefruit or grapefruit juice

Belgium
      AZ Sint-Jan, Brugge,  8000,  Belgium; Recruiting
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium; Recruiting
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands; Recruiting
      Academisch Ziekenhuis Utrecht, Utrecht,  3584 CX,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Isala Klinieken - locatie Sophia, Zwolle,  8000 GK,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Leyenburg Ziekenhuis, 's-Gravenhage,  2545 CH,  Netherlands; Recruiting
      Meander Medisch Centrum, Amersfoort,  3816 CP,  Netherlands; Recruiting
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  6525 GA,  Netherlands; Recruiting
      University Medical Center Rotterdam at Erasmus Medical Center, Rotterdam,  3000 CA,  Netherlands; Recruiting
      Vrije Universiteit Medisch Centrum, Amsterdam,  10P1HV,  Netherlands; Recruiting

Study chairs or principal investigators

J.J. Cornelissen, MD,  Study Chair,  Daniel Den Hoed Cancer Center at Erasmus Medical Center   

Study ID Numbers:  CDR0000069141; CKTO-2001-03; HOVON-51CML; EU-20132; HOVON-CKTO-2001-03; NOVARTIS-CST1571ANL01
Record last reviewed:  January 2002
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028847
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08