Glucarpidase Effect on Severe Delayed HDM-clearance in Children Treated With High-dose Mtx in ALL

Study Overview
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Brief Summary
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Early intervention in children and adolescents who experience delayed MTX-clearance and renal dysfunction in ALL treatments with the enzyme Glucarpidase which rapidly hydrolyses MTX to non-toxic metabolites to avoid life threatening complications.

Detailed Description
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The NOPHO ALL-2008 protocol is a treatment and research protocol that aims to improve the overall outcome of Nordic children and adolescents with ALL in comparison with the ALL-2000 protocol and with the aim to reduce and prevent toxic treatment complications with high-dose methotrexate (HD-MTX). The specific and primary objectives of the randomized study is: Early intervention in children and adolescents who experience delayed MTX-clearance and renal dysfunction with the enzyme Glucarpidase which rapidly hydrolyses MTX to non-toxic metabolites and lowers the serum concentration to avoid life threatening complications. Glucarpidase should be given if the 24 hour levels of MTX is > 250 µM, 36 hour levels > 30 µM or 42 hours levels > 10 µM together with a reduced kidney function. Glucarpidase treatment should take place within 48 hours from the start of HD-MTX treatment. To evaluate if the early intervention with Glucarpidase reduce the number of days the patients have to stay at the hospital. Evaluate the reduction of health costs of early intervention in patients with delayed MTX-clearance and renal dysfunction.

Official Title
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Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)

Conditions
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Acute Lymphoblastic Leukemia (ALL)

Intervention / Treatment
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* Drug: Glucarpidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children and adolescents who experience delayed MTX-clearance and renal dysfunction during high-dose methotrexate treatment in NOPHO ALL-2008. Exclusion Criteria: Children and adolescents with earlier anaphylactic reaction to Glucarpidase. Pregnant patients.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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: Glucarpidase arm<br>In the NOPHO ALL-2008 protocol patients with delayed methotrexate elimination (DME) in high-dose methotrexate treatments should be given Glucarpidase (50 ie/kg) with-in 60 hours from start of the methotrexate treatment. | Drug: Glucarpidase<br>* Patients treated with Glucarpidase if the 24 hour levels of MTX is >250 µM, 36 hour levels >30 µM or 42 hours levels >10 µM together with a reduced kidney function will be compared with patients in just below the tricking values.<br>* Other names: VORAXAZE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Event to HD-MTX Treatment in NOPHO ALL-2008 as a Measure of Toxic Mtx Concentrations in Blood, Nephrotoxicity, Hepatotoxicity, Mucositis, MTX Elimination Time and Permanent Kidney Damage. | Glucarpidase was used in case of predefined toxic MTX values at defined time points and/or in combination with decreased renal function. A total of 47 patients of the 1286 ALL-patients included in the protocol (3.7 %) were treated with Glucarpidase. | 6 years 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug: Glucarpidase