Acute Lymphoblastic Leukemia (ALL)Phase 3NOPHOCPG2NCT01305655
Glucarpidase Effect on Severe Delayed HDM-clearance in Children Treated With High-dose Mtx in ALL
A Phase 3 study testing Glucarpidase in people with Acute Lymphoblastic Leukemia (ALL), run by Nordic Society for Pediatric Hematology and Oncology at 5 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia (ALL)
- What is being tested?
- Glucarpidase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Jul 2008to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children and adolescents who experience delayed MTX-clearance and renal dysfunction during high-dose methotrexate treatment in NOPHO ALL-2008.
Who cannot join
- Children and adolescents with earlier anaphylactic reaction to Glucarpidase. Pregnant patients.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Sweden1 site
Department of Pediatrics, Drottning Sylvias Pediatric Hospital
Gothenburg
About this study
Official title: Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)
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.
Read the 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:
- 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.
- Conditions
- Acute Lymphoblastic Leukemia (ALL)
- Being tested
- Glucarpidase
- Keywords
- Drug: Glucarpidase
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucarpidaseDrug
Also called VORAXAZE®
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.
| Study group | Role | What they receive |
|---|---|---|
| Glucarpidase arm | Experimental | 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. Receives: Drug: Glucarpidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 years 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2011 (estimated)
- Study startJul 2008
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic Leukemia (ALL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordic Society for Pediatric Hematology and Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University Hospital
- Responsible party
- Principal investigator, Jesper Heldrup, Nordic Society for Pediatric Hematology and Oncology
- Investigators
- Jesper Heldrup, M D, Principal investigator, University Childrens hospital, Lund, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305655
- Sponsor's protocol ID
- NOPHO2008CPG2
- Acronym
- NOPHOCPG2
- Status last verified
- Aug 2018
- First submitted
- 28 Feb 2011
- Last updated
- 28 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Publication in preparation in Pediatric Blood and Cancer
Publications
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.
PubMed 27966809
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucarpidase (CPG2) Effect on Severe Delayed Methotrexate-clearance in Children Treated With High-dose Methotrexate in Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT01305655
- Acronym / sponsor ID
- NOPHOCPG2 / NOPHO2008CPG2
- Conditions
- Acute Lymphoblastic Leukemia (ALL)
- Keywords
- Drug: Glucarpidase
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Nordic Society for Pediatric Hematology and OncologyUniversity, hospital or other
- Collaborators
- Lund University Hospital
- Study start
- Jul 2008
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Mar 2011 (estimated)
- Results
- Posted 3 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glucarpidase arm | Experimental | Drug: GlucarpidaseIn 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. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Children and adolescents who experience delayed MTX-clearance and renal dysfunction during high-dose methotrexate treatment in NOPHO ALL-2008.
Key exclusion criteria (1 listed)
- Children and adolescents with earlier anaphylactic reaction to Glucarpidase. Pregnant patients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlucarpidaseAlso: VORAXAZE®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. | Drug | Glucarpidase arm |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27966809Svahn 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.
- Homepage of NOPHO - most areas are closedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Publication in preparation in Pediatric Blood and Cancer
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesper Heldrup, M D principal investigator
University Childrens hospital, Lund, Sweden
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glucarpidase in people with Acute Lymphoblastic Leukemia (ALL), run by Nordic Society for Pediatric Hematology and Oncology at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark, Finland, Iceland, Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 6 years 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01305655, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2018.