Clinical trial NCT01305655: Glucarpidase Effect on Severe Delayed HDM-clearance in Children Treated With High-dose Mtx in ALL
Official title: Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia (ALL)
Keywords: Drug: Glucarpidase
Lead sponsor: Nordic Society for Pediatric Hematology and Oncology
Sponsor class: OTHER
Collaborators: name: Lund University Hospital
First posted: 2011-03-01
Enrollment: 47
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 6 years 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Pediatrics, Rigshospitalet
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Reykjavik
country: Iceland
facility: University of Reykjavik
city: Trondheim
country: Norway
facility: University Hospital of Trondheim
city: Goteborg
country: Sweden
facility: Department of Pediatrics, Drottning Sylvias Pediatric Hospital
Study officials:
affiliation: University Childrens hospital, Lund, Sweden
name: Jesper Heldrup, M D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.