Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

July 22, 2015 updated by: University Health Network, Toronto

A Phase I Study Of Therapy With The Farnesyl Transferase Inhibitor R115777 (Zarnestra) Combined With Conventional Induction And Consolidation Chemotherapy For Previously Untreated Patients Over Age 55 With Acute Myeloid Leukemia (AML)

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with cytarabine and daunorubicin may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given with cytarabine and daunorubicin in treating older patients with acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin in older patients with previously untreated acute myeloid leukemia.
  • Determine the toxicity of this regimen in these patients.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of tipifarnib.

Induction therapy (1 course): Patients receive cytarabine IV continuously on days 1-7, daunorubicin IV on days 6-8, and oral tipifarnib twice daily on days 6-15 in the absence of unacceptable toxicity. Patients achieving complete remission proceed to consolidation therapy.

Consolidation therapy (1 course): After hematologic recovery, patients begin consolidation therapy 35-60 days after the start of induction therapy. Patients receive cytarabine, daunorubicin, and tipifarnib as in induction therapy.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the recommended phase II dose.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study within 1.5-22 months.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

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

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Children's Hospital at Hamilton Health Sciences
      • London, Ontario, Canada, N6A 465
        • London Regional Cancer Program at London Health Sciences Centre

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

56 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML)

    • All subtypes, except acute promyelocytic leukemia, are allowed
    • At least 20% bone marrow or peripheral blood blasts OR biopsy-confirmed extramedullary disease
  • No cerebrospinal fluid involvement

PATIENT CHARACTERISTICS:

Age

  • 56 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics
  • WBC < 100,000/mm^3 (treatment with hydroxyurea allowed)

Hepatic

  • Bilirubin ≤ 1.25 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.0 times ULN

Renal

  • Creatinine < 1.7 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • LVEF ≥ 50%
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Immunologic

  • HIV negative
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to tipifarnib or imidazole drugs (e.g., ketoconazole, clotrimazole, or miconazole)
  • No ongoing or active infection

Other

  • Not pregnant
  • Fertile patients must use effective contraception
  • Able to swallow oral medications
  • No other uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for AML except hydroxyurea for cytoreduction

  • More than 4 weeks since prior chemotherapy except hydroxyurea (6 weeks for nitrosoureas or mitomycin) and recovered

    • At least 24 hours since prior hydroxyurea

Endocrine therapy

  • No concurrent dexamethasone

Radiotherapy

  • More than 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy > 3,000 cGy to marrow-producing areas

Surgery

  • Not specified

Other

  • No other concurrent investigational agents
  • No other concurrent antileukemic agents

  • No concurrent treatment with any of the following:

    • Ketoconazole
    • Itraconazole
    • Voriconazole
    • Clarithromycin
    • Erythromycin
    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Cyclosporine
    • Pimozide
    • Warfarin
    • Grapefruit juice
    • Simvastatin
    • Lovastatin
    • Atorvastatin
  • No concurrent magnesium- or aluminum-containing antacids within 2 hours before or after tipifarnib administration

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
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Tipifarnib with conventional induction and consolidation
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: tipifarnib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin
Time Frame: minimum of 30 days per treatment cycle
minimum of 30 days per treatment cycle
Toxicity
Time Frame: All cycles
All cycles
Pharmacokinetics
Time Frame: Day 6
Day 6

Collaborators and Investigators

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

Sponsor

University Health Network, Toronto

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Joseph Brandwein, MD, Princess Margaret Hospital, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

April 1, 2007

Primary Completion (ACTUAL)

March 1, 2010

Study Registration Dates

First Submitted

January 7, 2005

First Submitted That Met QC Criteria

January 7, 2005

First Posted (ESTIMATE)

January 10, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

July 23, 2015

Last Update Submitted That Met QC Criteria

July 22, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMH-PHL-026
  • CDR0000405840 (REGISTRY: PDQ (Physician Data Query))
  • NCI-6670

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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