Leukemia
Conditions
Keywords
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
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.
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.
Interventions
DRUGtipifarnib
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
National Institutes of Health Clinical Center (CC)
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion 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
Countries
Australia, Canada, United States
Outcome results
None listed