A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine
I. To estimate the hematologic and cytogenetic response rate of newly diagnosed patients
with BCR/ABL (+) chronic myelogenous leukemia (CML) treated with combined homoharringtonine
(omacetaxine mepesuccinate) and low dose cytarabine.
II. To estimate the toxicity of these two drugs given in combination in a cooperative group
I. To assess duration of hematological response and incidence of hematological progression
for all patients.
II. To assess duration of cytogenetic response in patients continuing protocol therapy
beyond the initial nine months.
III. To use quantitative Southern blot monitoring of blood samples to monitor molecular
response rates in patients entered onto CALGB treatment studies for CML.
IV. To compare quantitative Southern blot results of blood samples with marrow cytogenetics
at the time of complete molecular response.
V. To use RT-PCR to monitor the frequency of residual disease in patients who have achieved
a complete blood Southern blot and marrow cytogenetic response (elimination of BCR/ABL
positivity by Southern blot and absence of the Philadelphia chromosome by cytogenetics).
Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous
infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses
of therapy in the absence of disease progression and unacceptable toxicity. Patients who are
major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor
cytogenetic responders are switched to interferon, and nonresponders are removed from
therapy and given the option to switch to interferon.
Patients are followed every 6 months for 10 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete cytogenetic, major cytogenetic, and hematologic response rate
Two separate single-stage Fleming designs will be used to test hypotheses regarding the major cytogenetic response rate and the complete cytogenetic response rate. Calculated and presented with their 95% confidence intervals.
Up to 9 months
Cancer and Leukemia Group B
United States: Food and Drug Administration
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