Acute Kidney InjuryNCT05899751
Retrospective Registry Study of Patients With Cancer Treated With High-dose Methotrexate
An observational study of Acute Kidney Injury and Drug Toxicity, run by Protherics Medicines Development Limited at 5 sites in 3 countries.
Trial summary
This retrospective observational study will evaluate high-dose methotrexate patterns of use, supportive care measures used during high-dose methotrexate chemotherapy, along with the incidence of delayed elimination of methotrexate, acute kidney injury and any associated impact of delayed elimination of methotrexate on… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Kidney Injury, Drug Toxicity
- What is being tested?
- High-dose methotrexate and Glucarpidase
- How many people
- 1,000 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 1 Apr 2022to Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study will be conducted at approximately 10 European sites where high-dose methotrexate infusions are administered. Sites will be selected to ensure a balanced accrual of children and adults treated with high-dose methotrexate.
Who may be able to join
- A diagnosis of any cancer from January 1, 2001 to June 30, 2021.
- Receipt of high-dose methotrexate chemotherapy, defined as a dose of 500 mg/m2 of body surface area or higher.
- Medical records available for review.
- Any age; any cancer type.
Who cannot join
- None.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Spain3 sites, 3 recruiting
- Recruiting
Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR)
Barcelona, 08035
Jennifer Lowe, +1 (214) 924 2117, jennifer.lowe@resonancehealth.org
Buck Cansino, +1 (210) 931-9433, buck.cansino@resonancehealth.org
- Recruiting
Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO)
Barcelona, 08035
Jennifer Lowe, +1 (214) 924 2117, jennifer.lowe@resonancehealth.org
Buck Cansino, 12109319433, buck.cansino@resonancehealth.org
- Recruiting
Hospital Universitario Reina Sofía
Córdoba, 14004
Jennifer Lowe, +1 (214) 924 2117, jennifer.lowe@resonancehealth.org
Buck Cansino, 12109319433, buck.cansino@resonancehealth.org
France1 site, 1 recruiting
- Recruiting
Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital
Marseille, 13354
Jennifer Lowe, +1 (214) 924 2117, jennifer.lowe@resonancehealth.org
Buck Cansino, 12109319433, buck.cansino@resonancehealth.org
Italy1 site, 1 recruiting
- Recruiting
University of Milan-Bicocca
Monza, 20900
Jennifer Lowe, +1 (214) 924 2117, jennifer.lowe@resonancehealth.org
Buck Cansino, 12109319433, buck.cansino@resonancehealth.org
About this study
Official title: High-dose Methotrexate Patterns of Use, Clearance, Toxicities, Supportive Care and Outcomes
This retrospective observational study will evaluate high-dose methotrexate patterns of use, supportive care measures used during high-dose methotrexate chemotherapy, along with the incidence of delayed elimination of methotrexate, acute kidney injury and any associated impact of delayed elimination of methotrexate on future courses of chemotherapy and disease outcomes in adults and children with cancer.
The study will compare current practice with existing guidelines and best practices to identify potential gaps in the management of high-dose methotrexate administration and delayed elimination of methotrexate. The study will identify variations in practice and outcomes in different study centers, countries, cancer types, patient age groups, by different methotrexate doses and infusion times and different supportive care measures used. The study will also document the proportion of high-dose methotrexate courses in which glucarpidase has been used and any toxicities attributable to the use of glucarpidase.
- Conditions
- Acute Kidney Injury, Drug Toxicity
- Being tested
- High-dose methotrexate, Glucarpidase
- Keywords
- Carboxypeptidases, Delayed Methotrexate Clearance, Hematologic Neoplasms, Hyperhydration, Leucovorin, Osteosarcoma
- Medical subject headings
- Acute Kidney Injury, Drug-Related Side Effects and Adverse Reactions, Hematologic Neoplasms, Water Intoxication, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose methotrexateDrug
High-dose methotrexate
GlucarpidaseDrug
Glucarpidase
| Study group | Role | What they receive |
|---|---|---|
| Patients Treated With High-dose Methotrexate | Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy. Receives: Drug: High-dose methotrexate; Drug: Glucarpidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delayed Elimination of Methotrexate
Incidence of delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined by Ramsey criteria.
Measured: 0-48 hours from the start of high-dose methotrexate infusion.
Acute Kidney Injury
Incidence of acute kidney injury of any grade after high-dose methotrexate chemotherapy.
Measured: 0-48 hours from the start of high-dose methotrexate infusion.
Severe Delayed Elimination of Methotrexate
Incidence of severe delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined as a methotrexate level ≥2 standard deviations above the population mean at 36, 42, or 48 hours from the start of high-dose methotrexate infusion and with the presence of acute kidney injury of any grade.
Measured: 0-48 hours from the start of high-dose methotrexate infusion.
Secondary outcomes (18)
Severity of Acute Kidney Injury
Severity of occurrences of acute kidney injury using CTCAE v5 criteria.
Measured: 0-48 hours from the start of high-dose methotrexate infusion.
Hospital Length of Stay
Duration of hospitalization.
Measured: Assessed through study completion, up to 2 years after enrollment.
Hospital Readmission
Incidence of hospital readmission.
Measured: Within 14 days of high-dose methotrexate infusion.
Delay of Subsequent Chemotherapy
Occurrence of delays to further blocks of chemotherapy resulting from delayed methotrexate elimination.
Measured: Within 14 days of high-dose methotrexate infusion.
Dose Reduction or Omission of Subsequent High-dose Methotrexate Therapy
Occurrence of dose reduction or omission of high-dose methotrexate from further cycles of chemotherapy resulting from delayed methotrexate elimination.
Measured: Within 14 days of high-dose methotrexate infusion.
Event-Free Survival
"Events" include death, relapse, abandonment, or refusal of treatment.
Measured: 3, 5, and 10 years.
Overall Survival
All-cause mortality as well as mortality separately due to disease progression or toxicity.
Measured: 3, 5, and 10 years.
Glucarpidase-Related Toxicity
Occurrence of toxicities associated with glucarpidase, including frequency, severity (using CTCAE v5 criteria) and including documenting any toxicities of grade 3 or higher.
Measured: 15 minutes post-glucarpidase through discharge.
Methotrexate Clearance after Glucarpidase
MTX levels.
Measured: 15 minutes post-glucarpidase through discharge.
Serum Creatinine Level
Renal function, as measured by serum creatinine level.
Measured: 15 minutes post-glucarpidase through discharge.
Use of Subsequent High-Dose Methotrexate After Glucarpidase
Occurrence of subsequent high-dose methotrexate chemotherapy cycles given after glucarpidase.
Measured: Within 14 days of high-dose methotrexate infusion.
Disease Outcome After Glucarpidase
Disease outcome after glucarpidase
Measured: 3, 5, and 10 years.
Use of Hyperhydration
Incidence of the use of hyperhydration supportive care measures during high-dose methotrexate chemotherapy.
Measured: Assessed at time of hospital discharge.
Use of Leucovorin
Incidence of the use of leucovorin during high-dose methotrexate chemotherapy.
Measured: Assessed at time of hospital discharge.
Use of Dialysis or Hemofiltration
Incidence of the use of dialysis or hemofiltration during high-dose methotrexate chemotherapy.
Measured: Assessed at time of hospital discharge.
Use of Oral Methotrexate Binders
Incidence of the use of oral methotrexate binders (cholestyramine, activated charcoal) during high-dose methotrexate chemotherapy.
Measured: Assessed at time of hospital discharge.
Creatinine Clearance
Renal function, as measured by creatinine estimate
Measured: 15 minutes post-glucarpidase through discharge.
Need for Dialysis
Renal function, as measured by need for dialysis.
Measured: 15 minutes post-glucarpidase through discharge.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start1 Apr 2022
- Primary completionAug 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Protherics Medicines Development Limited
- Sponsor type
- University, hospital or other
- Collaborators
- Resonance Health
- Responsible party
- Sponsor
- Investigators
- Carmelo Rizzari, MD, Principal investigator, University of Milano-Bicocca, Pediatric Hematology Oncology Unit MBBM Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05899751
- Sponsor's protocol ID
- PR001-CLN-pro101
- Status last verified
- Jun 2023
- First submitted
- 11 Apr 2023
- Last updated
- 10 May 2024
- Results posted
- No
Publications
Ramsey LB, Balis FM, O'Brien MM, Schmiegelow K, Pauley JL, Bleyer A, Widemann BC, Askenazi D, Bergeron S, Shirali A, Schwartz S, Vinks AA, Heldrup J. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. 2018 Jan;23(1):52-61. doi: 10.1634/theoncologist.2017-0243. Epub 2017 Oct 27.
PubMed 29079637Taylor ZL, Mizuno T, Punt NC, Baskaran B, Navarro Sainz A, Shuman W, Felicelli N, Vinks AA, Heldrup J, Ramsey LB. MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase. Clin Pharmacol Ther. 2020 Sep;108(3):635-643. doi: 10.1002/cpt.1957. Epub 2020 Jul 18.
PubMed 32558929
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Methotrexate Patterns of Use, Clearance, Toxicities, Supportive Care and Outcomes
- ClinicalTrials.gov ID
- NCT05899751
- Acronym / sponsor ID
- PR001-CLN-pro101
- Conditions
- Acute Kidney Injury, Drug Toxicity
- Keywords
- Carboxypeptidases, Delayed Methotrexate Clearance, Hematologic Neoplasms, Hyperhydration, Leucovorin, Osteosarcoma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Protherics Medicines Development LimitedUniversity, hospital or other
- Collaborators
- Resonance Health
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This retrospective observational study will evaluate high-dose methotrexate patterns of use, supportive care measures used during high-dose methotrexate chemotherapy, along with the incidence of delayed elimination of methotrexate, acute kidney injury and any associated impact of delayed elimination of methotrexate on future courses of chemotherapy and disease outcomes in adults and children with cancer.
The study will compare current practice with existing guidelines and best practices to identify potential gaps in the management of high-dose methotrexate administration and delayed elimination of methotrexate. The study will identify variations in practice and outcomes in different study centers, countries, cancer types, patient age groups, by different methotrexate doses and infusion times and different supportive care measures used. The study will also document the proportion of high-dose methotrexate courses in which glucarpidase has been used and any toxicities attributable to the use of glucarpidase.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients Treated With High-dose Methotrexate | – | Drug: High-dose methotrexate, Drug: GlucarpidasePatients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study will be conducted at approximately 10 European sites where high-dose methotrexate infusions are administered. Sites will be selected to ensure a balanced accrual of children and adults treated with high-dose methotrexate.
Key inclusion criteria (4 listed)
- A diagnosis of any cancer from January 1, 2001 to June 30, 2021.
- Receipt of high-dose methotrexate chemotherapy, defined as a dose of 500 mg/m2 of body surface area or higher.
- Medical records available for review.
- Any age; any cancer type.
Key exclusion criteria (1 listed)
- None.
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 |
|---|---|---|
| High-dose methotrexateHigh-dose methotrexate | Drug | Patients Treated With High-dose Methotrexate |
| GlucarpidaseGlucarpidase | Drug | Patients Treated With High-dose Methotrexate |
Primary outcome
Delayed Elimination of Methotrexate
Time frame: 0-48 hours from the start of high-dose methotrexate infusion.
Incidence of delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined by Ramsey criteria.
Acute Kidney Injury
Time frame: 0-48 hours from the start of high-dose methotrexate infusion.
Incidence of acute kidney injury of any grade after high-dose methotrexate chemotherapy.
Severe Delayed Elimination of Methotrexate
Time frame: 0-48 hours from the start of high-dose methotrexate infusion.
Incidence of severe delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined as a methotrexate level ≥2 standard deviations above the population mean at 36, 42, or 48 hours from the start of high-dose methotrexate infusion and with the presence of acute kidney injury of any grade.
18 secondary outcomes
Severity of Acute Kidney Injury
Time frame: 0-48 hours from the start of high-dose methotrexate infusion.
Hospital Length of Stay
Time frame: Assessed through study completion, up to 2 years after enrollment.
Hospital Readmission
Time frame: Within 14 days of high-dose methotrexate infusion.
Delay of Subsequent Chemotherapy
Time frame: Within 14 days of high-dose methotrexate infusion.
Dose Reduction or Omission of Subsequent High-dose Methotrexate Therapy
Time frame: Within 14 days of high-dose methotrexate infusion.
Event-Free Survival
Time frame: 3, 5, and 10 years.
Overall Survival
Time frame: 3, 5, and 10 years.
Glucarpidase-Related Toxicity
Time frame: 15 minutes post-glucarpidase through discharge.
Methotrexate Clearance after Glucarpidase
Time frame: 15 minutes post-glucarpidase through discharge.
Serum Creatinine Level
Time frame: 15 minutes post-glucarpidase through discharge.
Use of Subsequent High-Dose Methotrexate After Glucarpidase
Time frame: Within 14 days of high-dose methotrexate infusion.
Disease Outcome After Glucarpidase
Time frame: 3, 5, and 10 years.
Use of Hyperhydration
Time frame: Assessed at time of hospital discharge.
Use of Leucovorin
Time frame: Assessed at time of hospital discharge.
Use of Dialysis or Hemofiltration
Time frame: Assessed at time of hospital discharge.
Use of Oral Methotrexate Binders
Time frame: Assessed at time of hospital discharge.
Creatinine Clearance
Time frame: 15 minutes post-glucarpidase through discharge.
Need for Dialysis
Time frame: 15 minutes post-glucarpidase through discharge.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Background: PubMed 29079637Ramsey LB, Balis FM, O'Brien MM, Schmiegelow K, Pauley JL, Bleyer A, Widemann BC, Askenazi D, Bergeron S, Shirali A, Schwartz S, Vinks AA, Heldrup J. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. 2018 Jan;23(1):52-61. doi: 10.1634/theoncologist.2017-0243. Epub 2017 Oct 27.
- Background: PubMed 32558929Taylor ZL, Mizuno T, Punt NC, Baskaran B, Navarro Sainz A, Shuman W, Felicelli N, Vinks AA, Heldrup J, Ramsey LB. MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase. Clin Pharmacol Ther. 2020 Sep;108(3):635-643. doi: 10.1002/cpt.1957. Epub 2020 Jul 18.
- A pharmacokinetic model for the dose of methotrexate to display the concentration vs time curve for an individual patient overlaid upon the population-predicted curve for that dose.Link provided by the sponsor.
- Voraxaze Summary of Product Characteristics (SmPC)Link provided by the sponsor.
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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.
Carmelo Rizzari, MD principal investigator
University of Milano-Bicocca, Pediatric Hematology Oncology Unit MBBM Foundation
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Injury and Drug Toxicity, run by Protherics Medicines Development Limited at 5 sites in 3 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 4 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: status not confirmed, as of the sponsor's last update on 10 May 2024. 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 Spain, France, Italy. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lois Wallace (+1 945 239 1690, Lois.wallace@btgsp.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delayed Elimination of Methotrexate (time frame: 0-48 hours from the start of high-dose methotrexate infusion.). The study lists 3 primary outcomes in all. 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 NCT05899751, which also lists 2 linked publications.
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 10 May 2024.