A Phase I Study Of Therapy With The Farnesyl Transferase Inhibitor R115777 (Zarnestra) Combined With Conventional Induction And Consolidation Chemotherapy For Previously Untreated Patients Over Age 55 With Acute Myeloid Leukemia (AML)
- Determine the maximum tolerated dose of tipifarnib when administered with cytarabine
and daunorubicin in older patients with previously untreated acute myeloid leukemia.
- Determine the toxicity of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib.
Induction therapy (1 course): Patients receive cytarabine IV continuously on days 1-7,
daunorubicin IV on days 6-8, and oral tipifarnib twice daily on days 6-15 in the absence of
unacceptable toxicity. Patients achieving complete remission proceed to consolidation
Consolidation therapy (1 course): After hematologic recovery, patients begin consolidation
therapy 35-60 days after the start of induction therapy. Patients receive cytarabine,
daunorubicin, and tipifarnib as in induction therapy.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the
recommended phase II dose.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study within 1.5-22
Primary Purpose: Treatment
Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin
Joseph Brandwein, MD
Princess Margaret Hospital, Canada
United States: Food and Drug Administration