A Phase III Study of STI571 Versus Interferon-a (IFN-a) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
OBJECTIVES: I. Compare the time to treatment failure and overall survival in patients with
newly diagnosed, previously untreated, Philadelphia chromosome positive, chronic phase
chronic myelogenous leukemia treated with STI571 vs interferon alfa combined with
cytarabine. II. Compare the quality of life and disease and treatment related toxicities in
patients treated with these 2 regimens. III. Compare the rate and duration of complete
hematologic response (CHR) and major cytogenetic response (MCR) in patients treated with
these 2 regimens. IV. Compare the rate and duration of MCR and CHR attributable to crossover
therapy in patients who crossover to receive STI571 OR interferon alfa combined with
cytarabine. V. Compare the tolerability and safety of these regimens in these patients. VI.
Determine the population pharmacokinetics of STI571 in these patients.
OUTLINE: This is a randomized, open label, crossover, multicenter study. Patients are
randomized to one of two treatment arms: Arm I: Patients receive oral STI571 once daily. Arm
II: Patients receive interferon alfa (IFN-A) subcutaneously (SQ) daily. Gradual intrapatient
dose escalation is performed until the target dose of IFN-A is achieved. Patients then also
receive cytarabine SQ daily for 10 days every month. Cytarabine is discontinued when a
complete cytogenetic response is achieved and confirmed on two consecutive occasions not
more than 3 months apart. Both arms: Courses repeat monthly in the absence of progression to
accelerated phase or blast crisis, or unacceptable toxicity. Patients with no complete
hematologic response at 6 months, no major cytogenetic response at year 2, or loss of
complete hematologic response (without progression to accelerated or blastic phase)
discontinue treatment on the arm to which they were originally randomized and begin
treatment on the other arm. Crossover courses repeat monthly in the absence of progression
to accelerated phase or blast crisis, or unacceptable toxicity. Quality of life is assessed
prior to study; monthly for the first 6 months of study; at 9, 12, 18, and 24 months; at
time of crossover (if applicable); and at treatment discontinuation before year 2 (if
applicable). All patients are followed every 3 months for up to 8 years.
PROJECTED ACCRUAL: A total of 850 patients (425 per arm) will be accrued for this study.
Primary Purpose: Treatment
United States: Food and Drug Administration
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