Tipifarnib in Treating Young Patients With Refractory Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00022451
• Other study ID #: 010196
• Secondary ID: 01-C-0196CCOG-AD
• Status: Completed
• Phase: Phase 1
• First received: August 10, 2001
• Last updated: March 14, 2012
• Start date: June 2001
• Est. completion date: March 2005

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00017888

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• tipifarnib

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia
United States	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida
United States	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Riley Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Cancer Institute of New Jersey at Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	MBCCOP - South Texas Pediatrics	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	Children's Oncology Group, National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

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. Epub 2006 Aug 1. Review. — View Citation

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 refract — View Citation