Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as temozolomide, 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 temozolomide in treating young patients with refractory or recurrent leukemia.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and recommended phase II dose of temozolomide in pediatric patients with refractory or recurrent leukemia. Determine the toxic effects of this drug in these patients. Determine the pharmacokinetics of this drug in these patients. Secondary Determine the antitumor activity of this drug in these patients. Determine the biologic activity and mechanism(s) of resistance to this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18-24 months.

Official Title
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A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias

Conditions
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Leukemia

Intervention / Treatment
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* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed leukemia of any of the following types: Acute lymphoblastic leukemia Acute myeloid leukemia Chronic myelogenous leukemia in blast crisis Refractory or recurrent disease Immunophenotypic confirmation of disease at initial diagnosis or recurrence More than 25% blasts in the bone marrow (M3) Active extramedullary disease allowed except for leptomeningeal disease No known curative therapy or therapy proven to prolong survival with an acceptable quality of life No active CNS disease PATIENT CHARACTERISTICS: Age 1 to 21 Performance status Karnofsky 50-100% (for patients > 10 years of age) Lansky 50-100% (for patients ≤ 10 years of age) Life expectancy Not specified Hematopoietic WBC < 30,000/mm^3 (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator) Platelet count ≥ 20,000/mm^3 (platelet transfusions allowed) Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed) Hepatic ALT ≤ 5 times upper limit of normal (ULN) Albumin ≥ 2 g/dL Bilirubin ≤ 1.5 times ULN Renal Creatinine normal for age OR Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m^2 Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy At least 7 days since prior biologic therapy, including immunotherapy At least 3 months since prior stem cell transplantation No evidence of active graft-vs-host disease No concurrent biologic therapy No concurrent immunotherapy Chemotherapy Recovered from prior chemotherapy At least 6 weeks since prior nitrosoureas Prior therapy with hydroxyurea allowed for up to 24 hours before initiation of study drug No other concurrent chemotherapy Endocrine therapy Concurrent hydrocortisone or other corticosteroids allowed as premedications prior to blood product transfusions in patients with prior severe allergic reactions Radiotherapy Recovered from prior radiotherapy No concurrent radiotherapy Surgery Not specified Other No other concurrent anticancer agents No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 1 Year
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide Therapy<br> | Drug: temozolomide<br> <br> * Other names: NSC # 362856;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose and recommended phase II dose |  |  | 
| Toxicity as assessed by CTCAE 3.0 |  |  | 
| Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor activity |  |  | 
| Biologic activity and mechanisms of resistance |  |  | 

 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, childhood acute promyelocytic leukemia (M3), blastic phase chronic myelogenous leukemia