OBJECTIVES:

• Determine the maximum tolerated dose of homoharringtonine in patients with transformed phases of chronic myelogenous leukemia (CML). (Phase I completed as of 2/11/2004.)
• Determine the toxicity profile of this drug in these patients.
• Determine the response duration in patients with chronic phase CML treated with this drug.
• Compare the pharmacokinetics of this drug administered as a continuous infusion vs subcutaneously in these patients.

OUTLINE: This is a pilot, dose-escalation study. (Phase I completed as of 2/11/2004.)

• Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.
• Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of homoharringtonine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. An additional cohort of 25-30 patients with chronic phase chronic myelogenous leukemia receives remission induction and maintenance therapy as above at the MTD. (Phase I completed as of 2/11/2004.)

Patients are followed every 3 months.

PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic phase chronic myelogenous leukemia (CML), as defined by the following:

  • Less than 15% blasts in the peripheral blood (PB) or bone marrow (BM)
  • Less than 20% basophils in the PB or BM
  • Platelet count > 100,000/mm^3 (unless related to therapy)
  • Absence of clonal evolution* NOTE: * Patients with variant Philadelphia chromosome or deletions of chromosome Y (-Y) are eligible if there is no chromosomal change representing clonal evolution
• Philadelphia chromosome- OR BCR/ABL-positive disease by cytogenetics, fluorescence in situ hybridization, or polymerase chain reaction

• Failed prior therapy with imatinib mesylate, as defined by any of the following:

  • Failed to achieve or have lost a complete hematologic remission after 3 months of therapy
  • Failed to achieve or have lost at least a minimal cytogenetic response after 6 months of therapy
  • Failed to achieve or have lost a major or complete cytogenetic response after 12 months of therapy
  • Unable to tolerate imatinib mesylate despite adequate dose adjustment

• Failed no more than 2 prior treatment regimens (in addition to imatinib mesylate)

  • Treatment with hydroxyurea is not considered one regimen
• Ineligible for known regimens or protocols of higher efficacy or priority

PATIENT CHARACTERISTICS:

Age:

• 12 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• See Disease Characteristics