Glucarpidase Effect on Severe Delayed HDM-clearance in Children Treated With High-dose Mtx in ALL (NOPHOCPG2)
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)|
- 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.
- Evaluate Time at Hospital and Health Costs [ Time Frame: 6 years 6 months ]
|Study Start Date:||July 2008|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
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.
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 Name: VORAXAZE®
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01305655
|Department of Pediatrics, Rigshospitalet|
|Copenhagen, Denmark, DK-2100|
|Helsinki University Hospital|
|University of Reykjavik|
|University Hospital of Trondheim|
|Department of Pediatrics, Drottning Sylvias Pediatric Hospital|
|Principal Investigator:||Jesper Heldrup, M D||University Childrens hospital, Lund, Sweden|