Raltitrexed in Treating Children With Refractory Acute Leukemia

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of raltitrexed in treating children with refractory acute leukemia. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of raltitrexed given for three weeks to children with refractory acute leukemia. II. Determine the incidence and severity of other toxic effects of this regimen in these patients. III. Determine a safe and tolerable dose of raltitrexed, administered in this manner, to be used in phase II studies. IV. Determine the pharmacokinetics of this regimen in these patients. V. Determine if plasma 2' deoxyuridine concentrations are associated with raltitrexed toxicity or pharmacokinetics. VI. Evaluate the antitumor activity of raltitrexed against recurrent leukemia. OUTLINE: This is a dose escalation study. Patients receive raltitrexed intravenously over 15 minutes once weekly for 3 weeks followed by 1 week of rest. Treatment continues in the absence of disease progression and unacceptable toxicity. In the absence of dose-limiting toxicity (DLT) in the first cohort of 6 patients treated, subsequent cohorts of 6 patients each receive escalating doses of raltitrexed on the same schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Patients are followed every 6 months for 4 years, then annually thereafter.

Official Title
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A Phase I Trial of Tomudex in Children With Leukemia

Conditions
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Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: raltitrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven acute leukemia (M3 marrow) that is refractory to conventional therapy or for which no effective therapy exists No CNS leukemia No solid tumors Performance status: Karnofsky 50-100% OR Lansky at least 50 (for infants) Life expectancy: At least 8 weeks Bilirubin less than 1.5 mg/dL SGPT less than 5 times normal Normal creatinine for age OR GFR at least 70 mL/min No significant systemic illness such as infection No significant third space fluid collection Not pregnant or nursing Recovered from acute toxic effects of prior immunotherapy At least 6 months since prior bone marrow transplant with no evidence of graft-versus-host disease At least 10 days since prior biologic therapy At least 1 week since prior growth factors At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) and recovered No concurrent steroids Recovered from acute toxic effects of all prior radiotherapy At least 2 weeks since prior local palliative radiotherapy (small port) At least 6 months since prior substantial bone marrow radiation No other concurrent anticancer therapy or investigational agents No concurrent nonsteroidal anti-inflammatory agents

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive raltitrexed intravenously over 15 minutes once weekly for 3 weeks followed by 1 week of rest. Treatment continues in the absence of disease progression and unacceptable toxicity. | Drug: raltitrexed<br>* Given IV<br>* Other names: Tomudex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD based on incidence of DLT graded according to CTC version 2.0 |  | Up to 4 weeks |