Tipifarnib in Treating Young Patients With Refractory Leukemia

NCT ID: NCT00022451

Last Updated: 2012-03-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2001-06-30

Study Completion Date

2005-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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tipifarnib

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role lead

Principal Investigators

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Brigitte C. Widemann, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

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Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus

Atlanta, Georgia, United States

Site Status

MBCCOP-Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

Riley Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Site Status

Floating Hospital for Children

Boston, Massachusetts, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Cancer Institute of New Jersey at Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Columbus Children's Hospital

Columbus, Ohio, United States

Site Status

Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States

Site Status

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

Site Status

Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Texas Children's Cancer Center

Houston, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

MBCCOP - South Texas Pediatrics

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Australia Canada

References

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de Nigris F, Balestrieri ML, Napoli C. Targeting c-Myc, Ras and IGF cascade to treat cancer and vascular disorders. Cell Cycle. 2006 Aug;5(15):1621-8. doi: 10.4161/cc.5.15.3138. Epub 2006 Aug 1.

Reference Type BACKGROUND
PMID: 16921263 (View on PubMed)

Widemann BC, Arceci RJ, Jayaprakash N, Fox E, Zannikos P, Goodspeed W, Goodwin A, Wright JJ, Blaney SM, Adamson PC, Balis FM. Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Feb;56(2):226-33. doi: 10.1002/pbc.22775. Epub 2010 Sep 21.

Reference Type RESULT
PMID: 20860038 (View on PubMed)

Other Identifiers

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01-C-0196C

Identifier Type: -

Identifier Source: secondary_id

COG-ADVL0116

Identifier Type: -

Identifier Source: secondary_id

NCI-1930

Identifier Type: -

Identifier Source: secondary_id

CDR0000068819

Identifier Type: -

Identifier Source: secondary_id

010196

Identifier Type: -

Identifier Source: org_study_id

NCT00017888

Identifier Type: -

Identifier Source: nct_alias

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