Tipifarnib in Treating Young Patients With Refractory Leukemia

This study has been completed.
Sponsor:
Collaborators:
Children's Oncology Group
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00022451
First received: August 10, 2001
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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
Leukemia
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:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00022451

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

Additional Information:
Publications:
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:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014