Tipifarnib in Treating Young Patients With Refractory Leukemia

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Leukemia

Intervention / Treatment
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* Drug: tipifarnib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tipifarnib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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