Acute Lymphoblastic Leukemia (ALL)
Conditions
Keywords
Drug: Glucarpidase
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.
Interventions
DRUGGlucarpidase
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.
Sponsors
Lund University Hospital
Nordic Society for Pediatric Hematology and Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Countries
Denmark, Finland, Iceland, Norway, Sweden
Participant flow
Recruitment details
From July 2008 children treated with the NOPHO ALL 2008 protocol (1-18 years) in the Nordic- and Baltic countries received Glucarpidase if they had delayed Mtx elimination in connection HDMTX 5 g/sqr at predefined values.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 47 |
| Total | 47 |
Baseline characteristics
| Characteristic | Glucarpidase Arm |
|---|---|
| Age, Categorical <=18 years | 47 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 7.5 years STANDARD_DEVIATION 4.89 |
| Region of Enrollment Denmark | 11 participants |
| Region of Enrollment Finland | 1 participants |
| Region of Enrollment Iceland | 2 participants |
| Region of Enrollment Lithuania | 3 participants |
| Region of Enrollment Norway | 16 participants |
| Region of Enrollment Sweden | 14 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 47 |
| serious Total, serious adverse events | 0 / 47 |
Outcome results
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.
Time frame: 6 years 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glucarpidase Arm | 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. | 47 participants |