Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies — HDMTX  

Methotrexate Adverse Reaction Clinical Trial

Official title: Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Significant Impact Factors and Establishment of a Clinically Relevant Model

Status Completed

Clinical Trial Summary

* The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling.

Clinical Trial Description

• Methotrexate (MTX) is one of the critical components for treating all forms of acute lymphoblastic leukemia (ALL), which is the most common pediatric cancer. Unfortunately, high dose MTX has several undesirable side effects and MTX toxicity vastly differs from patient to patient.

• The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling.

• The final model was validated using nonparametric bootstrap analysis. Body surface area (BSA), pre-hydration, baseline serum creatinine and 24 h creatinine clearance rate were statistically significant covariates for distributional volume (V) and renal clearance (CL). Herein, is the first report of analysis of the importance of a series of patient factors on pharmacokinetics of MTX by one-compartment model. Using these data, we have established an efficient population pharmacokinetic model for MTX, which can be used to predict safe clinical application of MTX especially in children with ALL. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Leukemia, Lymphoid
• Methotrexate Adverse Reaction
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT02011022
• Study type: Interventional
• Source: The Children's Hospital of Zhejiang University School of Medicine
• Status: Completed
• Phase: N/A
• Start date: May 2009
• Completion date: February 2010