• Satey and Tolerability [ Designated as safety issue: Yes ]
  
• Dose-limiting toxicity [ Designated as safety issue: Yes ]
  
• Pharmacokinetics [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the safety and tolerability of arsenic trioxide and imatinib mesylate in patients with resistant chronic phase chronic myelogenous leukemia.
• Determine potential dose-limiting toxic effects in patients treated with this regimen.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily and arsenic trioxide IV over 1-2 hours on days 1-5 of week 1 and then twice weekly. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients (at least 6 patients for phase I and at least 12 patients for phase II) will be accrued for this study .

DISEASE CHARACTERISTICS:

• Cytogenetically confirmed Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting one of the following criteria:

  • Chronic phase

    • Less than 15% blasts in peripheral blood or marrow
    • Less than 30% blasts and promyelocytes in peripheral blood or marrow
    • Less than 20% basophils in blood or marrow
    • Platelet count at least 100,000/mm^3 (unless therapy related)
    • No progressive (increase of at least 10 cm in any 4 of the past 24 weeks) or existing (greater than 10 cm) splenomegaly

  • Complete hematologic response (CHR)

    • No immature myeloid cells in peripheral blood
    • No increased basophils in peripheral blood
    • WBC less than upper limit of normal (ULN)
    • Platelet count less than ULN

    • No major (less than 35% Ph+) or complete (0% Ph+) cytogenetic response after at least 6 months of imatinib mesylate

      • Loss of prior major cytogenetic response or failure to achieve major cytogenetic response

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin less than 1.5 times ULN
• AST or ALT less than 2.5 times ULN

Renal

• Creatinine less than 1.5 times ULN

Cardiovascular

• No New York Heart Association grade III or IV congestive heart failure
• No untreated symptomatic cardiac ischemia

• No underlying cardiac arrhythmia, including but not limited to any of the following:

  • Conduction abnormality/atrioventricular heart block
  • Nodal/junctional arrhythmia/dysrhythmia
  • Sinus bradycardia or tachycardia
  • Supraventricular tachycardia
  • Ventricular arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective barrier contraception during and for 3 months after study
• Electrolyte levels (especially potassium and magnesium) normal (CHR patients)
• No history of noncompliance that would preclude study participation
• No other concurrent serious, uncontrolled medical condition
• No grade 2 or greater neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 14 days since prior therapy except hydroxyurea, anagrelide hydrochloride, or imatinib mesylate
• More than 28 days since prior investigational agents
• No concurrent grapefruit or grapefruit juice