Pharmacokinetic Analysis of High Dose Methotrexate in Ped... | NCT02011022

Studies
Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

NCT02011022

Sponsor

The Children's Hospital of Zhejiang University School of Medicine

Status

Completed

Last Update Posted

Dec 13, 2013Estimated

Enrollment

291Actual

Phase

Not Applicable

Conditions

Methotrexate Adverse Reaction

Interventions

3g MTX
5g MTX

Countries

China

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Dec 2013

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

May 2009

Primary Completion Date

Dec 2009Actual

Completion Date

Feb 2010Actual

First Submitted Date

Dec 5, 2013

First Submission Date that Met QC Criteria

Dec 10, 2013

First Posted Date

Dec 13, 2013Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Dec 10, 2013

Last Update Posted Date

Dec 13, 2013Estimated

Sponsor/Collaborators Module

Responsible Party, by Official Title

Weiqun Xu, Doctor, The Children's Hospital of Zhejiang University School of MedicinePrincipal Investigator

Lead Sponsor

The Children's Hospital of Zhejiang University School of MedicineOTHER

Collaborators

Not provided

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

291Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
3g group	Experimental	The dose of MTX is 3 g/m2	Drug: 3g MTX
5g group	Experimental	The dose of MTX is 5g/m2	Drug: 5g MTX

Interventions

Name	Type	Description	Arm Group Labels	Other Names
3g MTX	Drug	The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL	3g group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
elimination delay	The serum MTX is higher than 1umol/L in 48 hours or 0.1umol/L in 96 hours	3 days

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

Not provided

Maximum Age

18 Years

Standard Ages

ChildAdult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Weiqun Xu	The Children's Hospital of Zhejiang University School of Medicine	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
The Children's Hospital of Zhejiang University School of Medicine		Hangzhou	Zhejiang	310006	China

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24241962	Background	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.

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms