Know Cancer

forgot password

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

Phase 1
21 Years
Not Enrolling

Thank you

Trial Information

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



- 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.


- 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

Inclusion Criteria


- 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



- 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


- Not required to be normal


- Bilirubin normal

- SGPT and SGOT normal

- No significant hepatic dysfunction

- No grade 3 or 4 liver function test results within the past month


- Creatinine normal OR

- Creatinine clearance at least 60 mL/min

- No significant renal dysfunction


- No significant cardiac dysfunction


- No significant pulmonary dysfunction


- No history of grand mal seizures grade 3 or greater except febrile seizures

- No persistent sensory or motor neuropathy greater than grade 2


- 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,

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


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


- 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)


- At least 4 weeks since prior radiotherapy

- No concurrent radiotherapy


- Not specified


- 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

- No other concurrent investigational agents

- No concurrent retinoids

- No concurrent anticonvulsants

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Brigitte C. Widemann, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

June 2001

Completion Date:

March 2005

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • relapsing chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic myelogenous leukemia, BCR-ABL1 positive
  • childhood acute promyelocytic leukemia (M3)
  • acute undifferentiated leukemia
  • juvenile myelomonocytic leukemia
  • childhood chronic myelogenous leukemia
  • Leukemia



Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Children's Hospital of Michigan Detroit, Michigan  48201
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
NYU School of Medicine's Kaplan Comprehensive Cancer Center New York, New York  10016
Huntsman Cancer Institute Salt Lake City, Utah  84112
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
CCOP - Columbia River Oncology Program Portland, Oregon  97225
CCOP - Scott and White Hospital Temple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
MBCCOP - LSU Health Sciences Center New Orleans, Louisiana  70112
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's Hospital of Orange County Orange, California  92668
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Mercy Hospital Kansas City, Missouri  64108
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
Floating Hospital for Children Boston, Massachusetts  02111
Cardinal Glennon Children's Hospital Saint Louis, Missouri  63104
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort Worth Fort Worth, Texas  76104
Texas Children's Cancer Center Houston, Texas  77030-2399
City of Hope Comprehensive Cancer Center Duarte, California  91010
UCSF Comprehensive Cancer Center San Francisco, California  94115
St. Louis Children's Hospital Saint Louis, Missouri  63110
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City, Kansas  66160-7353
Herbert Irving Comprehensive Cancer Center at Columbia University New York, New York  10032
Oklahoma University Medical Center Oklahoma City, Oklahoma  73104
Stanford Cancer Center at Stanford University Medical Center Stanford, California  94305
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
CCOP - Marshfield Clinic Research Foundation Marshfield, Wisconsin  54449
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus Atlanta, Georgia  30342
Shands Cancer Center at the University of Florida Health Science Center Gainesville, Florida  32610-0296
MBCCOP-Medical College of Georgia Cancer Center Augusta, Georgia  30912-4000
Riley Children Cancer Center at Riley Hospital for Children Indianapolis, Indiana  46202-5225
Cancer Center at Hackensack University Medical Center Hackensack, New Jersey  07601
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Vanderbilt Children's Hospital Nashville, Tennessee  37232-6310
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390-9063
MBCCOP - South Texas Pediatrics San Antonio, Texas  78229-3900
Columbus Children's Hospital Columbus, Ohio  43205-2696
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182