Retrospective Registry Study of Patients With Cancer Treated With High-dose Methotrexate

Acute Kidney Injury Clinical Trial

Official title:

High-dose Methotrexate Patterns of Use, Clearance, Toxicities, Supportive Care and Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05899751
• Other study ID #: PR001-CLN-pro101
• Status: Recruiting
• Start date: April 1, 2022
• Est. completion date: December 2024

Study information

• Verified date: June 2023
• Source: BTG International Inc.
• Contact: Lois Wallace
• Phone: +1 945 239 1690
• Email: Lois.wallace[@]btgsp.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• None.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Drug Toxicity
• Drug-Related Side Effects and Adverse Reactions

Intervention

Drug:
• High-dose methotrexate
High-dose methotrexate
• Glucarpidase
Glucarpidase

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital	Marseille
Italy	University of Milan-Bicocca	Monza
Spain	Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR)	Barcelona
Spain	Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO)	Barcelona
Spain	Hospital Universitario Reina Sofía	Córdoba

Sponsors (2)

Lead Sponsor	Collaborator
Protherics Medicines Development Limited	Resonance Health

Countries where clinical trial is conducted

France,  Italy,  Spain, 

References & Publications (2)

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. — View Citation

Taylor 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delayed Elimination of Methotrexate	Incidence of delayed elimination of methotrexate after high-dose methotrexate chemotherapy, defined by Ramsey criteria.	0-48 hours from the start of high-dose methotrexate infusion.
Primary	Acute Kidney Injury	Incidence of acute kidney injury of any grade after high-dose methotrexate chemotherapy.	0-48 hours from the start of high-dose methotrexate infusion.
Primary	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.	0-48 hours from the start of high-dose methotrexate infusion.
Secondary	Severity of Acute Kidney Injury	Severity of occurrences of acute kidney injury using CTCAE v5 criteria.	0-48 hours from the start of high-dose methotrexate infusion.
Secondary	Hospital Length of Stay	Duration of hospitalization.	Assessed through study completion, up to 2 years after enrollment.
Secondary	Hospital Readmission	Incidence of hospital readmission.	Within 14 days of high-dose methotrexate infusion.
Secondary	Delay of Subsequent Chemotherapy	Occurrence of delays to further blocks of chemotherapy resulting from delayed methotrexate elimination.	Within 14 days of high-dose methotrexate infusion.
Secondary	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.	Within 14 days of high-dose methotrexate infusion.
Secondary	Event-Free Survival	"Events" include death, relapse, abandonment, or refusal of treatment.	3, 5, and 10 years.
Secondary	Overall Survival	All-cause mortality as well as mortality separately due to disease progression or toxicity.	3, 5, and 10 years.
Secondary	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.	15 minutes post-glucarpidase through discharge.
Secondary	Methotrexate Clearance after Glucarpidase	MTX levels.	15 minutes post-glucarpidase through discharge.
Secondary	Serum Creatinine Level	Renal function, as measured by serum creatinine level.	15 minutes post-glucarpidase through discharge.
Secondary	Use of Subsequent High-Dose Methotrexate After Glucarpidase	Occurrence of subsequent high-dose methotrexate chemotherapy cycles given after glucarpidase.	Within 14 days of high-dose methotrexate infusion.
Secondary	Disease Outcome After Glucarpidase	Disease outcome after glucarpidase	3, 5, and 10 years.
Secondary	Use of Hyperhydration	Incidence of the use of hyperhydration supportive care measures during high-dose methotrexate chemotherapy.	Assessed at time of hospital discharge.
Secondary	Use of Leucovorin	Incidence of the use of leucovorin during high-dose methotrexate chemotherapy.	Assessed at time of hospital discharge.
Secondary	Use of Dialysis or Hemofiltration	Incidence of the use of dialysis or hemofiltration during high-dose methotrexate chemotherapy.	Assessed at time of hospital discharge.
Secondary	Use of Oral Methotrexate Binders	Incidence of the use of oral methotrexate binders (cholestyramine, activated charcoal) during high-dose methotrexate chemotherapy.	Assessed at time of hospital discharge.
Secondary	Creatinine Clearance	Renal function, as measured by creatinine estimate	15 minutes post-glucarpidase through discharge.
Secondary	Need for Dialysis	Renal function, as measured by need for dialysis.	15 minutes post-glucarpidase through discharge.

External Links

•   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.
•   Voraxaze Summary of Product Characteristics (SmPC)