Renal and Hepatic Clearance Following High-Dose Methotrexate in Childhood ALL

NCT01896752 | Completed

• 1 other identifier: R35-A1642-10S7
• Study Type: observational
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

High-dose methotrexate therapy (HDMTX) is an important part of treatment of childhood acute lymphoblastic leukemia (ALL). HDMTX would be improved substantially if it were possible to predict the clearance of MTX for each patient and use this to tailor an individualized dosing of the drug. However, only about 3.7, 0.2, and 2% of the inter-individual variation in MTX clearance is explained by age, gender and ancestry, respectively. Genetic variation seems to explain about 10% of this difference, and SNPs in genes encoding transporter proteins (e.g. organic anion transporter 1B1 (OATP1B1) and reduced folate carrier (RFC)) are suggested to have a particular large impact. A serious limitation to the applicability of SNPs in prediction of MTX pharmacokinetics, however, is the substantial intra-individual variation in MTX clearance. The intra-individual variation in MTX clearance is related to renal function but a large amount of a HDMTX dose also enters the liver, where it is metabolized to 7-hydroxy MTX and probably also undergoes enterohepatic circulation. Thus, the aim of this study is to determine the role of the liver and renal function in MTX pharmacokinetics, and evaluate the predictive potential of pharmacogenetic (e.g. the rfc SNP) and pharmacokinetic parameters of MTX elimination during HDMTX.

Conditions

Lymphoblastic Leukemia, Acute, Childhood

Outcome Measures

Primary Outcomes (1)

• clearance

  within the first 6 months after recruitment has been completed

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

All children diagnosed and treated for Acute Lymphoblastic Leukemia, ALL, at Rigshospitalet during the last two years, i.e. 43 children, and who will receive HD-MTX during the study period.

You may qualify if:

• Admitted to Rigshospitalet
• Diagnosed with ALL
• Receiving high dose MTX

You may not qualify if:

• Above 19 years of age

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Danish Cancer Society: collaborator

Study Sites (1)

Department of Pediatrics, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood for RFC allele determination; serum for determination of concentration of MTX, clearances, and other pharmacokinetic parameters; urine for determination of concentration of MTX and clearances, and other pharmacokinetic parameters

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kjeld Schmiegelow, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: March 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

DK (1)