Tipifarnib in Treating Young Patients With Refractory Leukemia - Full Text View

Sponsor:	National Cancer Institute (NCI)
Collaborator:	Children's Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00022451

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: tipifarnib	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I Trial and Pharmacokinetic Study of R115777 in Pediatric Patients With Refractory Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: R 115777 Tipifarnib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

June 2001

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00022451

Hide Study Locations

Locations

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

Sponsors and Collaborators

National Cancer Institute (NCI)

Children's Oncology Group

Investigators

Study Chair:	Brigitte C. Widemann, MD	NCI - Pediatric Oncology Branch
Study Chair:	Brigitte C. Widemann, MD	NCI - Pediatric Oncology Branch

Study ID Numbers:	CDR0000068819, NCI-01-C-0196C, COG-ADVL0116, NCI-1930
Study First Received:	August 10, 2001
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00022451 History of Changes
Health Authority:	United States: Federal Government