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

NCT05899751 | Unknown

• 1 other identifier: PR001-CLN-pro101
• Study Type: observational
• Target: 1,000
• Locations: 3 countries
• Sites: 5

Brief 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.

Conditions

Acute Kidney Injury; Drug Toxicity

Keywords

Carboxypeptidases; Delayed Methotrexate Clearance; Hematologic Neoplasms; Hyperhydration; Leucovorin; Osteosarcoma

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (18)

• Severity of Acute Kidney Injury

  0-48 hours from the start of high-dose methotrexate infusion.

• Hospital Length of Stay

  Assessed through study completion, up to 2 years after enrollment.

• Hospital Readmission

  Within 14 days of high-dose methotrexate infusion.

• Delay of Subsequent Chemotherapy

  Within 14 days of high-dose methotrexate infusion.

• Dose Reduction or Omission of Subsequent High-dose Methotrexate Therapy

  Within 14 days of high-dose methotrexate infusion.

Study Arms (1)

Patients Treated With High-dose Methotrexate

Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy.

Drug: High-dose methotrexate; Drug: Glucarpidase

Interventions

High-dose methotrexate DRUG

High-dose methotrexate

Patients Treated With High-dose Methotrexate

Glucarpidase DRUG

Glucarpidase

Patients Treated With High-dose Methotrexate

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• None.

Sponsors & Collaborators

• Protherics Medicines Development Limited: lead
• Resonance Health: collaborator

Study Sites (5)

Assistance Publique Hôpitaux de Marseille (APHM), La Timone Hospital

Marseille, 13354, France

RECRUITING

University of Milan-Bicocca

Monza, 20900, Italy

RECRUITING

Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca (VHIR)

Barcelona, 08035, Spain

RECRUITING

Fundación Privada Instituto de Investigación Oncológica de Vall d'Hebron (VHIO)

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

RECRUITING

Related 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.

  PMID: 29079637 BACKGROUND

• 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.

  PMID: 32558929 BACKGROUND

Related 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)

MeSH Terms

Conditions

Acute Kidney Injury; Drug-Related Side Effects and Adverse Reactions; Hematologic Neoplasms; Water Intoxication; Osteosarcoma

Interventions

Methotrexate; glucarpidase

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chemically-Induced Disorders; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Poisoning; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Carmelo Rizzari, MD

  University of Milano-Bicocca, Pediatric Hematology Oncology Unit MBBM Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lois Wallace

CONTACT

+1 945 239 1690; Lois.wallace@btgsp.com

Jennie Molland

CONTACT

+44 1239 851122; Jennie.molland@btgsp.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: June 12, 2023
• Study Start: April 1, 2022
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: May 10, 2024

Record last verified: 2023-06

Locations

FR (1); IT (1); ES (3)