Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide in treating young patients with leukemia or lymphoma.

Detailed Description
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OBJECTIVES: Determine the toxic effects of arsenic trioxide in pediatric patients with refractory leukemia or lymphoma. Determine the maximum tolerated dose of this drug in this patient population. Determine the plasma pharmacokinetics of this drug in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease (acute promyelocytic leukemia [APL] vs non-APL). Stratum I (APL patients): Patients receive standard-dose arsenic trioxide IV over 2 hours daily 5 days a week for 4 weeks. Treatment continues every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Stratum II (Non-APL patients): Cohorts of 3-6 patients receive escalating doses of arsenic trioxide (according to the stratum 1 schedule above) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with arsenic trioxide at the recommended phase II dose. Leukemia patients in both strata without progressive disease who have not achieved complete remission after the first 20 doses may continue to receive arsenic trioxide for 2 additional weeks. Patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for stratum I of this study within 2-3 years. A total of 3-30 patients will be accrued for stratum II of this study within 1-2 years.

Official Title
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Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: arsenic trioxide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed leukemia or lymphoma refractory to standard curative treatment regimens Measurable or evaluable disease No meningeal leukemia or lymphoma No HIV-related lymphoma No lymphoproliferative diseases PATIENT CHARACTERISTICS: Age: 2 to 21 Acute promyelocytic leukemia (APL) patients (stratum I) must be age 2 to 12 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin normal SGPT less than 2 times upper limit of normal No significant hepatic dysfunction that would preclude study therapy Renal: Creatinine normal (age adjusted) OR Creatinine clearance at least 60 mL/min Potassium, magnesium, and calcium at least lower limit of normal (oral or IV supplementation allowed) No significant renal dysfunction that would preclude study therapy Cardiovascular: Rate corrected QTc interval no greater than 0.48 on EKG No significant cardiac dysfunction that would preclude study therapy No cardiac disease, including dysrhythmias Pulmonary: No significant pulmonary dysfunction that would preclude study therapy Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No persistent grade 3 or greater sensory or motor neuropathy No prior grand mal seizures (grade 3 or greater) within the past 2 years other than febrile seizures (except for patients with APL at discretion of investigator) No clinically significant unrelated systemic illness that would preclude study therapy (e.g., serious infection) HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], and epoetin alfa) No concurrent immunotherapy Chemotherapy: No prior arsenic trioxide At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered No concurrent intrathecal chemotherapy except for acute promyelocytic leukemia (APL) patients experiencing progressive meningeal leukemia and demonstrating benefit from arsenic trioxide for systemic disease No other concurrent anticancer chemotherapy Endocrine therapy: No concurrent steroids (except corticosteroids for retinoic acid syndrome) Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: At least 6 months since prior anticonvulsants At least 1 week since prior retinoid therapy No concurrent retinoids No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 2 Years
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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: arsenic trioxide|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 myeloid leukemia, childhood acute promyelocytic leukemia (M3), recurrent childhood acute lymphoblastic leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative