Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

March 19, 2015 updated by: National Cancer Institute (NCI)

Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.

SECONDARY OBJECTIVES:

I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.

III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.

OUTLINE: This is a multicenter study.

Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.

After completion of study therapy, patients are followed up every 30 days.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Blood and Marrow Transplant Group of Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University/Winship Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10065
        • Weill Medical College of Cornell University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Previously untreated acute myeloid leukemia (AML) (de novo or secondary)

    • No diagnosis of acute promyelocytic leukemia (APL)
  • Deemed unsuitable for or refuses standard induction chemotherapy
  • RASGRP1:APTX ratio >= 5, through bone marrow screening
  • No patients with known leukemic involvement of the central nervous system
  • ECOG performance status =< 2
  • No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
  • 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 (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
  • ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
  • 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
  • No symptomatic neuropathy of grade 2 or worse
  • No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
  • No 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 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 CD4 cell count >= 400/mm^3 are eligible
  • No other concurrent cytotoxic or biologic antileukemic therapy
  • No patients who are receiving any other investigational agents

  • Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated

    • If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission (CR) Rate
Time Frame: From first treatment through follow up period, an expected average of 12 months
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.
From first treatment through follow up period, an expected average of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Overall Survival (OS)
Time Frame: From first treatment through follow up period, an expected average of 12 months
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).
From first treatment through follow up period, an expected average of 12 months
Median 1-Year Survival Rate
Time Frame: 1 year
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.
1 year
Number of Participants With Relapse Free Survival
Time Frame: 7 months
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.
7 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jeffrey Lancet, Moffitt Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

May 24, 2011

First Submitted That Met QC Criteria

May 25, 2011

First Posted (Estimate)

May 26, 2011

Study Record Updates

Last Update Posted (Estimate)

April 8, 2015

Last Update Submitted That Met QC Criteria

March 19, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2011-02589 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U01CA070095 (U.S. NIH Grant/Contract)
  • N01CM00071 (U.S. NIH Grant/Contract)
  • P30CA076292 (U.S. NIH Grant/Contract)
  • N01CM00100 (U.S. NIH Grant/Contract)
  • 16572
  • CDR0000699713
  • 8977 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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