Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

NCT ID: NCT02011022

Last Updated: 2013-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

291 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2010-02-28

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.

Conditions

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Methotrexate Adverse Reaction

Keywords

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Methotrexate, Pharmacokinetic Acute lymphoblastic leukemia Model

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

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3g group

The dose of MTX is 3 g/m2

Group Type EXPERIMENTAL

3g MTX

Intervention Type DRUG

The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL

5g group

The dose of MTX is 5g/m2

Group Type EXPERIMENTAL

5g MTX

Intervention Type DRUG

The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients

Interventions

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3g MTX

The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL

Intervention Type DRUG

5g MTX

The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients

Intervention Type DRUG

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
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Children's Hospital of Zhejiang University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Weiqun Xu

Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Weiqun Xu

Role: PRINCIPAL_INVESTIGATOR

The Children's Hospital of Zhejiang University School of Medicine

Locations

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The Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Countries

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China

References

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Yanagimachi M, Goto H, Kaneko T, Naruto T, Sasaki K, Takeuchi M, Tanoshima R, Kato H, Yokosuka T, Kajiwara R, Fujii H, Tanaka F, Goto S, Takahashi H, Mori M, Kai S, Yokota S. Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy. Int J Hematol. 2013 Dec;98(6):702-7. doi: 10.1007/s12185-013-1464-z. Epub 2013 Nov 16.

Reference Type BACKGROUND
PMID: 24241962 (View on PubMed)

Related Links

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Other Identifiers

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chzj-HDMTX-20131205

Identifier Type: -

Identifier Source: org_study_id