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

NCT ID: NCT01305655

Last Updated: 2018-09-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2014-12-31

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:

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.

Conditions

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Acute Lymphoblastic Leukemia (ALL)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Glucarpidase

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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VORAXAZE®

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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lund University Hospital

OTHER

Sponsor Role collaborator

Nordic Society for Pediatric Hematology and Oncology

OTHER

Sponsor Role lead

Responsible Party

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Jesper Heldrup

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jesper Heldrup, M D

Role: PRINCIPAL_INVESTIGATOR

University Childrens hospital, Lund, Sweden

Locations

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Department of Pediatrics, Rigshospitalet

Copenhagen, , Denmark

Site Status

Helsinki University Hospital

Helsinki, , Finland

Site Status

University of Reykjavik

Reykjavik, , Iceland

Site Status

University Hospital of Trondheim

Trondheim, , Norway

Site Status

Department of Pediatrics, Drottning Sylvias Pediatric Hospital

Gothenburg, , Sweden

Site Status

Countries

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Denmark Finland Iceland Norway Sweden

References

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Svahn T, Mellgren K, Harila-Saari A, Asberg A, Kanerva J, Jonsson O, Vaitkeviciene G, Stamm Mikkelssen T, Schmiegelow K, Heldrup J. Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia. Pediatr Blood Cancer. 2017 Jul;64(7). doi: 10.1002/pbc.26395. Epub 2016 Dec 14.

Reference Type DERIVED
PMID: 27966809 (View on PubMed)

Other Identifiers

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NOPHO2008CPG2

Identifier Type: -

Identifier Source: org_study_id

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