Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

Study Overview
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Brief Summary
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* 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.

Detailed Description
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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.

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

Conditions
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Methotrexate Adverse Reaction

Intervention / Treatment
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* Drug: 3g MTX
* Drug: 5g MTX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute lymphoblastic leukemia and non-hodgkin's lymphoma younger than 18 years old Exclusion Criteria: Non lymphoblastic malignancies or older than 18 years

Ages Eligible for Study
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Maximum Age: 18 Years

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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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3g group<br>The dose of MTX is 3 g/m2 | Drug: 3g MTX<br>* The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL<br>|
| Experimental: 5g group<br>The dose of MTX is 5g/m2 | Drug: 5g MTX<br>* The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| elimination delay | The serum MTX is higher than 1umol/L in 48 hours or 0.1umol/L in 96 hours | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate,, Pharmacokinetic, Acute lymphoblastic leukemia, Model