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

Phase 3

Completed

• Conditions: Acute Lymphoblastic Leukemia (ALL)
• Interventions: Drug: Glucarpidase

• Registration Number: NCT01305655
• Lead Sponsor: Nordic Society for Pediatric Hematology and Oncology

Brief Summary

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

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:

1. 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.

2. To evaluate if the early intervention with Glucarpidase reduce the number of days the patients have to stay at the hospital.

3. Evaluate the reduction of health costs of early intervention in patients with delayed MTX-clearance and renal dysfunction.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2011-02-28
• Study First Submitted QC: 2011-02-28
• Study First Posted: 2011-03-01
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Results First Submitted: 2016-10-17
• Results First Submitted QC: 2016-12-10
• Results First Posted: 2017-02-03
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-31
• Last Update Posted: 2018-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

Children and adolescents who experience delayed MTX-clearance and renal dysfunction during high-dose methotrexate treatment in NOPHO ALL-2008.

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Exclusion Criteria

Children and adolescents with earlier anaphylactic reaction to Glucarpidase. Pregnant patients.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Glucarpidase arm	Glucarpidase	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.

Primary Outcome Measures

Name	Time	Method
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.	6 years 6 months	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.

Trial Locations

Locations (5)

Helsinki University Hospital; 🇫🇮 Helsinki, Finland

Department of Pediatrics, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

University Hospital of Trondheim; 🇳🇴 Trondheim, Norway

University of Reykjavik; 🇮🇸 Reykjavik, Iceland

Department of Pediatrics, Drottning Sylvias Pediatric Hospital; 🇸🇪 Goteborg, Sweden