Tipifarnib in Treating Young Patients With Refractory Leukemia

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00022451

Collaborator

National Cancer Institute (NCI) (NIH), Children's Oncology Group (Other)

Locations

Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: tipifarnib	Phase 1

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 Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2001

Actual Study Completion Date :

Mar 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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