Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies (HDMTX)

Zhejiang University

Status: Completed

Conditions: Methotrexate Adverse Reaction

Treatments: Drug: 5g MTX; Drug: 3g MTX

Study type: Interventional

Funder types: Other

Identifiers

NCT02011022

chzj-HDMTX-20131205

Details and patient eligibility

About

* 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.

Full 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.

Enrollment: 291 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

291 participants in 2 patient groups

3g group

Experimental group

Description:

The dose of MTX is 3 g/m2

Treatment:

Drug: 3g MTX

5g group

Experimental group

Description:

The dose of MTX is 5g/m2

Treatment:

Drug: 5g MTX