Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

Methotrexate Adverse Reaction Clinical Trial

— HDMTX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02011022
• Other study ID #: chzj-HDMTX-20131205
• Status: Completed
• Phase: N/A
• First received: December 5, 2013
• Last updated: December 10, 2013
• Start date: May 2009
• Est. completion date: February 2010

Study information

• Verified date: December 2013
• Source: The Children's Hospital of Zhejiang University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

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.

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 information / eligibility

• Status: Completed
• Enrollment: 291
• Est. completion date: February 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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

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

Intervention

Drug:
• 3g MTX
The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL
• 5g MTX
The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients

Locations

Country	Name	City	State
China	The Children's Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
The Children's Hospital of Zhejiang University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	elimination delay	The serum MTX is higher than 1umol/L in 48 hours or 0.1umol/L in 96 hours	3 days	Yes

External Links

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