Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia
I. 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.) II.
Determine the toxicity profile of this drug in these patients. III. Determine the response
duration in patients with chronic phase CML treated with this drug.
IV. 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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|