Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

March 22, 2013 updated by: National Cancer Institute (NCI)

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 Leukemia

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.

Study Type

Interventional

Enrollment (Actual)

125

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
    • Maryland
      • Baltimore, Maryland, United States, 21287-8936
        • Johns Hopkins University

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:

  • Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
  • ECOG performance status 0 or 1
  • Patients must be able to give informed consent
  • SGOT and SGPT =< 2.5 x normal limits (grade 1)
  • Serum creatinine =< 1.5 x normal limits (grade 1)

  • AML (any of the following):

    • Newly diagnosed AML in adults >= 75 years
    • Newly diagnosed AML arising from MDS in adults >= 65 years
  • Hyperleukocytosis with >= 30,000 leukemic blasts/uL

Exclusion Criteria:

  • Acute promyelocytic (FAB M3) subtype
  • Previously treated with chemotherapy for leukemia (except for hydroxyurea)
  • Disseminated intravascular coagulation (laboratory or clinical)
  • Active central nervous system leukemia
  • Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
  • Intrinsic impaired organ function (as stated above)
  • Symptomatic neuropathy (grade 2 or worse)
  • Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole
  • Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (tipifarnib)
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission (CR) rate
Time Frame: Up to 8 years
CR rates will be calculated with 95% confidence intervals for each age group separately.
Up to 8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Partial remission (PR) rate
Time Frame: Up to 8 years
Will be estimated by observed proportions and 95% confidence intervals.
Up to 8 years
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.
Up to 8 years
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.
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 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.
From time of enrollment onto this study to the time of death, assessed up to 8 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

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

October 1, 2001

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

December 7, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

March 25, 2013

Last Update Submitted That Met QC Criteria

March 22, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02980
  • U01CA070095 (U.S. NIH Grant/Contract)
  • U01CA069854 (U.S. NIH Grant/Contract)
  • UMGCC 0116

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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