Methotrexate Early Toxicity Monitoring (METoxiM)

Methotrexate Early Toxicity Monitoring in Primary Central Nervous System Lymphomas (PCNSL)

High-dose methotrexate (MTX) is the main componement of first line treatment in primary central nervous system lymphoma. Renal toxicity is the main dose limiting toxicity because of major MTX elimination by the kidneys. MTX crystallizes in renal tubules, leading to a renal failure (RF) and further delaying its elimination. When RF occurs, MTX accumulates, prolonging the duration of treatment exposure. MTX prolonging exposure can cause life-threatening complications and delay further treatments in the patient. Preventive measures have been developped, such as alkaline fluid hyperhydration and folic acid administration, to try to reduce the risk of these adverse events.

In suspected severe RF in link to MTX is suspected, glucarpidase can be administared. However, this is an expensive treatment and not all patients recover normal renal function despite its use.

MTX is an essential treatment for the management of PCNSL which is currently a curable disease especially in patients who are able to receive a consolidation treatment as thiotepa-based intensive consolidation followed by autologous stem cell transplantation (IC-ASCT). IC-ASCT requires a normal renal function, which could be impaired by severe RF secondary to MTX.

The purpose of the study is to investigate how early dosing MTX could be used to simulate late concentrations. Early monitoring of MTX elimination could be implemented to identify patients at risk of delayed elimination and thus introduce rapid mesures as early administration of glucarpidase.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Central Nervous System Lymphoma
• Intervention / Treatment: Other: methotrexate plasmatic dosing

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laurence SCHENONE; Phone Number: +33 04 91 38 55 00; Email: Laurence.SCHENONE@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Assistance Publique - Hopitaux de Marseille
    • Contact: Laurence SCHENONE
    • Principal Investigator: Laurence SCHENONE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patient aged 18 years or older,
• Patient with a primary lymphoma of the central nervous system, histologically or cytologically proven,
• Patient eligible for high-dose methotrexate treatment (> at 500 mg/m 2), in the first line of treatment,
• Patient who has received information regarding the study and signed an informed consent,
• Patient beneficiary or entitled to a social security scheme.

Exclusion Criteria:

• Patient treated with a therapy complementary to the standard 1st-line treatment based on high-dose MTX as part of a clinical research protocol,
• Patient in a period of exclusion from another research protocol at the time of signing consent,
• Subjects covered by articles L1121-5 to 1121-8 of the Public Health Code (minor patient, adult patient under guardianship or curatorship, patient deprived of liberty, pregnant or breastfeeding woman).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients suffering from primary central nervous system lymphomas PCNSL	Other: methotrexate plasmatic dosing; Methotrexate (MTX) dosage at 2,4,6,8,24 and 48 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy measurement of Bayesian model	Determine, in patients with Primary Central Nervous System Lymphoma (PCNL), the most efficient Bayesian model for predicting the delay in MTX elimination using a pharmacometry approach (in silico modeling based on a population approach) based on the early dosage of methotrexate in plasma.	48 hours post MTX

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Bayesian model for predicting renal toxicity of MTX T48H using a pharmacometric approach (in silico modeling) based on early dosing of methotrexate in plasma	Renal toxicity shall be defined as acute renal failure graded according to CTCAE V5 in relation to the value of serum creatinine before administration of MTX.	48 hours post MTX
Determine the bayesian model for predicting MTX clearance 72 hours after MTX using a pharmacometric approach (in silico modeling) based on early dosing of methotrexate in plasma	Delay in elimination will be defined by a methotrexate dosage 72 hours after administration (T72H) beyond 0.2 μmol/L.	72 hours post MTX
Estimate in an exploratory approach the performance of the Bayesian model for predicting the delay in MTX elimination at 48 hours using a pharmacometric approach (in silico modeling)	Correlation between, early dosage of methotrexate in plasma and other parameters of interest measured at baseline (before MTX administration) such as patient age, albumin and creatinine clearance.	48 hours post
Estimate in an exploratory approach the performance of the Bayesian model for predicting overexposure to MTX at 48 hours using a pharmacometric approach (in silico modeling)	Correlation between, early dosage of methotrexate in plasma and other parameters of interest measured at baseline (before MTX administration) such as patient age, albumin and creatinine clearance. Overexposure to MTX is defined by a measured T48H > 10 μmol/L.	48 hours post MTX

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François Crémieux, Assistance Publique - Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: RCAPHM24_0313; ID RCB: 2025-A01802-47 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No