Tipifarnib in Treating Young Patients With Refractory Leukemia

March 14, 2012 updated by: National Institutes of Health Clinical Center (CC)

A Phase I Trial and Pharmacokinetic Study of R115777 in Pediatric Patients With Refractory Leukemia

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of tipifarnib in treating young patients who have refractory leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and toxicity profile of tipifarnib in pediatric patients with refractory leukemia.
  • Determine the pharmacokinetics of this drug in these patients.
  • Determine the toxicity profile of this drug in these patients.

Secondary

  • Analyze the gene expression profile of leukemic blasts from these patients before and after treatment with this drug.
  • Determine circulating levels of nerve growth factor and correlate these levels with clinical neurotoxicity from this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral tipifarnib every 12 hours on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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 at least 2 of 6 patients experience dose-limiting toxicity. At least 9 additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 12-34 patients will be accrued for this study within 1-2 years.

Study Type

Interventional

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

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
      • Montreal, Quebec, Canada, H3G 1A4
        • Montreal Children's Hospital at McGill University Health Center
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94143
        • UCSF Comprehensive Cancer Center
      • Stanford, California, United States, 94305-5208
        • Stanford Cancer Center at Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • Shands Cancer Center at the University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
      • Augusta, Georgia, United States, 30912-4000
        • MBCCOP-Medical College of Georgia Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5225
        • Riley Children Cancer Center at Riley Hospital for Children
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-7223
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0914
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Cancer Center at Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Columbus, Ohio, United States, 43205-2696
        • Columbus Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126
        • Oklahoma University Medical Center
    • Oregon
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4318
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213-2583
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Hollings Cancer Center at Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38105-2794
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232-6310
        • Vanderbilt Children's Hospital
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229-3900
        • MBCCOP - South Texas Pediatrics
      • Temple, Texas, United States, 76508
        • CCOP - Scott and White Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • Marshfield, Wisconsin, United States, 54449
        • CCOP - Marshfield Clinic Research Foundation
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

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

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed acute lymphoblastic leukemia, acute nonlymphoblastic leukemia, juvenile myelomonocytic leukemia (JMML), or chronic myelogenous leukemia (CML) in blast crisis

    • Refractory to standard curative therapy
    • Acute promyelocytic leukemia refractory to tretinoin and arsenic trioxide
    • Philadelphia chromosome-positive CML refractory to imatinib mesylate
  • Greater than 25% blasts in bone marrow (M3 bone marrow) except for patients with JMML
  • Active extramedullary disease allowed
  • No active leptomeningeal leukemia

PATIENT CHARACTERISTICS:

Age:

  • 21 and under

Performance status:

  • Karnofsky 50-100% (over 10 years of age)
  • Lansky 50-100% (10 years of age and under)

Life expectancy:

  • Not specified

Hematopoietic:

  • Not required to be normal

Hepatic:

  • Bilirubin normal
  • SGPT and SGOT normal
  • No significant hepatic dysfunction
  • No grade 3 or 4 liver function test results within the past month

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min
  • No significant renal dysfunction

Cardiovascular:

  • No significant cardiac dysfunction

Pulmonary:

  • No significant pulmonary dysfunction

Neurologic:

  • No history of grand mal seizures grade 3 or greater except febrile seizures
  • No persistent sensory or motor neuropathy greater than grade 2

Other:

  • No clinically significant unrelated systemic illness
  • No serious infection
  • No organ dysfunction that would preclude study participation
  • No requirement for total parenteral nutrition
  • No known allergy to azoles (e.g., clotrimazole, fluconazole, ketoconazole, voriconazole)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 1 week since prior colony-stimulating factor therapy (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa
  • At least 3 months since prior myeloablative therapy followed by bone marrow or stem cell transplantation
  • No concurrent immunotherapy
  • No concurrent GM-CSF or interleukin-11

Chemotherapy:

  • At least 2 weeks since prior chemotherapy
  • No concurrent intrathecal chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • At least 1 week since prior corticosteroids
  • No concurrent corticosteroids (except for acute allergic reaction)

Radiotherapy:

  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • Recovered from nonhematologic toxicity of all prior therapy
  • At least 1 week since prior retinoids
  • No antacids (magnesium- or aluminum-containing formulations) within 2 hours of study drug
  • No other concurrent investigational agents
  • No concurrent retinoids
  • No concurrent anticonvulsants

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
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)
Children's Oncology Group

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

June 1, 2001

Study Completion (Actual)

March 1, 2005

Study Registration Dates

First Submitted

August 10, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

March 15, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 010196
  • 01-C-0196C
  • COG-ADVL0116
  • NCI-1930
  • CDR0000068819

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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