Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Tipifarnib in Treating Young Patients With Refractory Leukemia

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.

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: 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

Relevance to patient case: not relevant