Glucarpidase Effect on Severe Delayed HDM-clearance in Children Treated With High-dose Mtx in ALL (NOPHOCPG2)

August 31, 2018 updated by: Jesper Heldrup, Nordic Society for Pediatric Hematology and Oncology

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Department of Pediatrics, Rigshospitalet
  • Finland
      • Helsinki, Finland
        • Helsinki University Hospital
  • Iceland
      • Reykjavik, Iceland
        • University of Reykjavík
  • Norway
      • Trondheim, Norway
        • University Hospital of Trondheim
  • Sweden
      • Goteborg, Sweden
        • Department of Pediatrics, Drottning Sylvias Pediatric Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glucarpidase arm
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
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.
Other Names:
  • VORAXAZE®

What is the study measuring?

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.
Time Frame: 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.
6 years 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nordic Society for Pediatric Hematology and Oncology

Collaborators

Lund University Hospital

Investigators

  • Principal Investigator: Jesper Heldrup, M D, University Childrens hospital, Lund, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

February 28, 2011

First Submitted That Met QC Criteria

February 28, 2011

First Posted (Estimate)

March 1, 2011

Study Record Updates

Last Update Posted (Actual)

September 28, 2018

Last Update Submitted That Met QC Criteria

August 31, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NOPHO2008CPG2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Publication in preparation in Pediatric Blood and Cancer

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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