Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia

Commissie Voor Klinisch Toegepast Onderzoek

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Leukemia

Treatments: Drug: imatinib mesylate; Drug: cytarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT00028847

HOVON-CKTO-2001-03

CDR0000069141

HOVON-51CML

NOVARTIS-CST1571ANL01

EU-20132

CKTO-2001-03

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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