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

Acute Lymphoblastic Leukemia (ALL) Clinical Trial

— NOPHOCPG2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01305655
• Other study ID #: NOPHO2008CPG2
• Status: Completed
• Phase: Phase 3
• Start date: July 2008
• Est. completion date: December 2014

Study information

• Verified date: August 2018
• Source: Nordic Society for Pediatric Hematology and Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Denmark	Department of Pediatrics, Rigshospitalet	Copenhagen
Finland	Helsinki University Hospital	Helsinki
Iceland	University of Reykjavik	Reykjavik
Norway	University Hospital of Trondheim	Trondheim
Sweden	Department of Pediatrics, Drottning Sylvias Pediatric Hospital	Goteborg

Sponsors (2)

Lead Sponsor	Collaborator
Nordic Society for Pediatric Hematology and Oncology	Lund University Hospital

Countries where clinical trial is conducted

Denmark,  Finland,  Iceland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Homepage of NOPHO - most areas are closed