A Phase II Study of Farnesyl Transferase Inhibitor R115777 (Zarnestra) (R115777 ( Zarnestra), Tipifarnib, R115777, NSC #702818) in Elderly Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
I. To determine the complete response rate of R115777 (tipifarnib) in previously untreated
acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >=
65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.
I. To determine progression-free and overall survival in patients with previously untreated
AML treated with R115777, using a chronic dosing schedule.
II. To determine the duration of response in patients with previously untreated AML treated
with R115777, using a chronic dosing schedule.
III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein
kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
(PI3K) in leukemic cells.
IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.
V. To determine the toxicities of R115777 when given in a chronic dosing schedule.
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or
partial response, hematologic improvement, or stable disease continue treatment every 29-63
days in the absence of disease progression or unacceptable toxicity. Patients with a
complete response after the second course of therapy receive 2 additional courses of
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete remission (CR) rate
CR rates will be calculated with 95% confidence intervals for each age group separately.
Up to 8 years
Johns Hopkins University
United States: Food and Drug Administration
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