Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)
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
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 > 20 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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Denmark: Danish Medicines Agency