Tipifarnib in Treating Young Patients With Refractory Leukemia

This study has been completed.
Children's Oncology Group
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
First received: August 10, 2001
Last updated: March 14, 2012
Last verified: March 2012

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
Drug: tipifarnib
Phase 1

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

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Study Start Date: June 2001
Study Completion Date: March 2005
Detailed Description:



  • 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 years.


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


  • 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, voriconazole)
  • 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 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

  Show 61 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Study Chair: Brigitte C. Widemann, MD National Cancer Institute (NCI)
  More Information

Additional Information:
ClinicalTrials.gov Identifier: NCT00022451     History of Changes
Obsolete Identifiers: NCT00017888
Other Study ID Numbers: 010196, 01-C-0196C, COG-ADVL0116, NCI-1930, CDR0000068819
Study First Received: August 10, 2001
Last Updated: March 14, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
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

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014