A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 84
- Locations
- 5
- Primary Endpoint
- Complete Response
Study Overview
Brief Summary
This randomized phase II trial is studying the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, 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 etoposide may kill more cancer cells.
Detailed Description
OBJECTIVES:
I. To compare the efficacy and toxicity of two schedules of tipifarnib plus etoposide as induction therapy in older patients with newly diagnosed, previously untreated acute myeloid leukemia.
II. To study mechanisms of leukemia cell resistance to tipifarnib in combination with etoposide.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •ECOG performance status 0-2
- •Serum creatinine =< 2.0 mg/dL
- •SGOT and SGPT =< 3 times upper limit of normal
- •Bilirubin =< 2 mg/dL
Exclusion Criteria
- •Active, uncontrolled infection
- •Patients with infection under active treatment and controlled with antimicrobials are eligible
- •Presence of other life-threatening illnesses
- •Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
- •Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
Arms & Interventions
Arm I
Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
Intervention: tipifarnib (Drug)
Arm I
Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
Intervention: etoposide (Drug)
Arm II (closed to accrual as of November 2008)
Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10.
Intervention: tipifarnib (Drug)
Arm II (closed to accrual as of November 2008)
Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10.
Intervention: etoposide (Drug)
Outcomes
Primary Outcomes
Complete Response
Time Frame: 6 months
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/mcL and a platelet count of 100,000 mcL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.
Secondary Outcomes
No secondary outcomes reported