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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Kidney Injury, Drug Toxicity

Intervention / Treatment
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* Drug: High-dose methotrexate
* Drug: Glucarpidase


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients Treated With High-dose Methotrexate<br>Patients with a diagnosis of any cancer receiving high-dose methotrexate chemotherapy. | Drug: High-dose methotrexate<br>* High-dose methotrexate<br>Drug: Glucarpidase<br>* Glucarpidase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| Hospital Length of Stay | Duration of hospitalization. | Assessed through study completion, up to 2 years after enrollment. | 
| Hospital Readmission | Incidence of hospital readmission. | 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. | 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. | Within 14 days of high-dose methotrexate infusion. | 
| Event-Free Survival | Events include death, relapse, abandonment, or refusal of treatment. | 3, 5, and 10 years. | 
| Overall Survival | All-cause mortality as well as mortality separately due to disease progression or toxicity. | 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. | 15 minutes post-glucarpidase through discharge. | 
| Methotrexate Clearance after Glucarpidase | MTX levels. | 15 minutes post-glucarpidase through discharge. | 
| Serum Creatinine Level | Renal function, as measured by serum creatinine level. | 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. | Within 14 days of high-dose methotrexate infusion. | 
| Disease Outcome After Glucarpidase | Disease outcome after glucarpidase | 3, 5, and 10 years. | 
| Use of Hyperhydration | Incidence of the use of hyperhydration supportive care measures during high-dose methotrexate chemotherapy. | Assessed at time of hospital discharge. | 
| Use of Leucovorin | Incidence of the use of leucovorin during high-dose methotrexate chemotherapy. | Assessed at time of hospital discharge. | 
| Use of Dialysis or Hemofiltration | Incidence of the use of dialysis or hemofiltration during high-dose methotrexate chemotherapy. | 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. | Assessed at time of hospital discharge. | 
| Creatinine Clearance | Renal function, as measured by creatinine estimate | 15 minutes post-glucarpidase through discharge. | 
| Need for Dialysis | Renal function, as measured by need for dialysis. | 15 minutes post-glucarpidase through discharge. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carboxypeptidases, Delayed Methotrexate Clearance, Hematologic Neoplasms, Hyperhydration, Leucovorin, Osteosarcoma