Zarnestra in Newly Diagnosed Acute Myelogenous Leukemia (AML)With 2 Gene Expression Signature Ratio
The purpose of this study is to determine the ability of a new test to predict whether patients will benefit from treatment with R115777 (ZARNESTRA, also called Tipifarnib). R115777 is an orally dosed, medication that inhibits the activity of the Farnesyl Transferase protein. Scientific experiments have suggested that R115777 can inhibit the function of proteins that play a role in the development of leukemia, and clinical studies of R115777 in humans has demonstrated that it can induce complete remissions (CR) in approximately 8-20% of patients with AML. R115777 is an investigational or experimental anticancer agent that has not yet been approved by the Food and Drug Administration for use in Acute Myelogenous Leukemia (AML).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio|
- Complete Remission (CR) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
- Median Overall Survival (OS) [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).
- Median 1-Year Survival Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.
- Number of Participants With Relapse Free Survival [ Time Frame: 7 months ] [ Designated as safety issue: No ]Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||April 2014|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: R115777 Therapy
Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
All screened participants with an RASGRP1:APTX ratio ≥ 5 will be eligible for a R115777 treatment course of a maximum of 6 cycles. Treatment will be administered on an outpatient basis.
This study will test the ability of a newly developed screening test, the RASGRP1:aprataxin (APTX) ratio, to identify patients who are more likely to benefit from R115777 therapy. RASGRP1 and APTX are genes that are expressed in leukemia cells. This test is performed on a sample of bone marrow tissue, and determines the ratio of RASGRP1 and APTX expression in the bone marrow. Ratios that are C5 are will be considered as a positive result, and these patients will be eligible for treatment with R115777. The ratio of C5 is expected to be found in about 30% of patients. This screening test is still considered an experimental procedure.
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Emory - Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Medical Center|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|Johns Hopkins Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21231|
|University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|United States, New Jersey|
|Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08901|
|United States, New York|
|Cornell - Weill Medical College of Cornell University|
|New York, New York, United States, 10065|
|United States, North Carolina|
|UNC-Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Jeffrey Lancet, M.D.||H. Lee Moffitt Cancer Center and Research Institute|