Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia
RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with cytarabine and daunorubicin may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given with cytarabine and daunorubicin in treating older patients with acute myeloid leukemia.
Drug: daunorubicin hydrochloride
|Study Design:||Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin [ Time Frame: minimum of 30 days per treatment cycle ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: All cycles ] [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2007|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
|Experimental: Tipifarnib with conventional induction and consolidation||Drug: cytarabine Drug: daunorubicin hydrochloride Drug: tipifarnib|
- 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 therapy.
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 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00101153
|McMaster Children's Hospital at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8N 3Z5|
|London Regional Cancer Program at London Health Sciences Centre|
|London, Ontario, Canada, N6A 465|
|Study Chair:||Joseph Brandwein, MD||Princess Margaret Hospital, Canada|