Zarnestra in Newly Diagnosed Acute Myelogenous Leukemia (AML)With 2 Gene Expression Signature Ratio

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01361464
First received: May 24, 2011
Last updated: September 10, 2014
Last verified: September 2014

May 24, 2011
September 10, 2014
May 2011
December 2012   (final data collection date for primary outcome measure)
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.
Number of Participants with Complete Remission [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]
To determine the complete remission (CR) rate in AML patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. Patients will be periodically followed after their completion of the study to collect information on subsequent therapies and survival data.
Complete list of historical versions of study NCT01361464 on ClinicalTrials.gov Archive Site
  • 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.
  • Median Overall Survival (OS) Rate [ 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 CRF.
  • Median 1-Year Survival Rate [ Time Frame: Up to 12 months per participant ] [ Designated as safety issue: No ]
    One year survival will be calculated from Kaplan Meier estimates.
  • Number of Serious Adverse Events Reported That May be Related to Study Treatment [ Time Frame: From first treatment through follow up period, an expected average of 7 months ] [ Designated as safety issue: Yes ]
    All patients receiving R115777 will be evaluable for toxicity from the time of their first treatment with R115777, up through the 30-day follow up period after treatment termination, or until the initiation of subsequent therapy, whichever comes first.
Not Provided
Not Provided
 
Zarnestra in Newly Diagnosed Acute Myelogenous Leukemia (AML)With 2 Gene Expression Signature Ratio
Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 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).

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myelogenous Leukemia
Drug: R115777
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.
Other Names:
  • Zarnestra™
  • NSC # 702818
  • Tipifarnib
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.
Intervention: Drug: R115777
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
21
March 2015
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age ≥ 65 with previously untreated AML (de novo or secondary)
  • Deemed unsuitable for or refuses standard induction chemotherapy
  • RASGRP1:APTX ratio ≥5, through bone marrow screening
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Patients must have normal organ function as defined below:
  • Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 1
  • Total bilirubin less than 1.5 times ULN (CTC Grade 1), unless the increase is unequivocally due to hemolysis or Gilbert's Syndrome
  • Alanine transaminase (ALT) and aspartate transaminase (AST) less than 2.5 times ULN (CTC Grade 1)
  • Ability to understand and the willingness to sign a written informed consent document
  • The effects of R115777 (ZARNESTRA) on the developing human fetus are unknown. For this reason and because farnesyl transferase inhibitor (FTI) agents as well as other therapeutic agents used in this trial are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Diagnosis of acute promyelocytic leukemia (APL)
  • Patients who are receiving any other investigational agents
  • Patients with known leukemic involvement of the central nervous system
  • Patients with white blood cells (WBC) ≥ 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
  • Symptomatic neuropathy of grade 2 or worse
  • Uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777, such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole or terconazole
  • Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking R115777 is contraindicated. If clinically indicated, subjects may use nonenzyme-inducing anticonvulsants during treatment with R115777.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Known HIV-positive patients NOT on antiretroviral therapy AND with a cluster of differentiation 4 (CD4) cell count ≥ 400/mm³ are eligible.
Both
65 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01361464
NCI # 8977, MCC-16572
Yes
H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
Principal Investigator: Jeffrey Lancet, M.D. H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP