Clinical Trial: Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Le

Brief Summary: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 therapy.

Patients are followed for survival.

CR rates will be calculated with 95% confidence intervals for each age group separately.



Original Primary Outcome:

Current Secondary Outcome:

  • Partial remission (PR) rate [ Time Frame: Up to 8 years ]
    Will be estimated by observed proportions and 95% confidence intervals.
  • Toxicity rates assessed using NCI CTCAE version 3.0 [ Time Frame: Up to 8 years ]
    Will be estimated by observed proportions and 95% confidence intervals.
  • Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 8 years ]
    Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
  • Duration of survival [ Time Frame: From time of enrollment onto this study to the time of death, assessed up to 8 years ]
    Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 7, 2001
Date Started: October 2001
Date Completion:
Last Updated: March 22, 2013
Last Verified: March 2013