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Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

Not Applicable
Completed
Conditions
Methotrexate Adverse Reaction
Interventions
Drug: 3g MTX
Drug: 5g MTX
Registration Number
NCT02011022
Lead Sponsor
The Children's Hospital of Zhejiang University School of Medicine
Brief 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.

Detailed 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
291
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
3g group3g MTXThe dose of MTX is 3 g/m2
5g group5g MTXThe dose of MTX is 5g/m2
Primary Outcome Measures
NameTimeMethod
elimination delay3 days

The serum MTX is higher than 1umol/L in 48 hours or 0.1umol/L in 96 hours

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

The Children's Hospital of Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

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