Clinical trial NCT02011022: Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies
Official title: Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Significant Impact Factors and Establishment of a Clinically Relevant Model
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Methotrexate Adverse Reaction
Keywords: Methotrexate,
Pharmacokinetic
Acute lymphoblastic leukemia
Model
Lead sponsor: The Children's Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
First posted: 2013-12-13
Enrollment: 291
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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

Primary outcomes:
measure: elimination delay
timeFrame: 3 days
Secondary outcomes:
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: The Children's Hospital of Zhejiang University School of Medicine
name: Weiqun Xu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.