Methotrexate Early Toxicity Monitoring

NCT07406230 | Not Yet Recruiting

• 2 other identifiers: RCAPHM24_0313ID RCB: 2025-A01802-47
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  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

  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)

  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)

  48 hours post MTX

Study Arms (1)

Patients suffering from primary central nervous system lymphomas PCNSL

EXPERIMENTAL

Other: methotrexate plasmatic dosing

Interventions

methotrexate plasmatic dosing OTHER

Methotrexate (MTX) dosage at 2,4,6,8,24 and 48 hours

Patients suffering from primary central nervous system lymphomas PCNSL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patient treated with a therapy complementary to the standard 1st-line treatment based on high-dose MTX as part of a clinical research protocol,
• 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).

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

Location

Study Officials

• François Crémieux

  Assistance Publique - Hôpitaux de Marseille

  STUDY DIRECTOR

Central Study Contacts

Laurence SCHENONE

CONTACT

04 91 38 55 00; Laurence.SCHENONE@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 12, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

FR (1)