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Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy


N/A
18 Years
N/A
Not Enrolling
Both
Central Nervous System Neoplasms, Lymphoma, Large B-Cell, Diffuse, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma

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Trial Information

Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy


MTX is a substrate of MRP2, a renal tubular transporter encoded by the ABCC2 gene. It has
been shown that single nucleotide polymorphisms (SNPs) on the ABCC2 gene are associated with
impairment of MTX elimination. Mutations on the ABCC2 gene are also responsible for the
Dubin-Johnson syndrome, characterised by the absence of a functional MRP2 protein. Apart
from hyperbilirubinaemia, the main biological perturbation observed in this disease is a
typical increase of the urinary ratio of coproporphyrins I (I+ III) (UCP ratio). Our
hypothesis is that the UCP ratio could be used as a biomarker of MRP2's activity, thus
predicting MTX elimination. One hundred patients treated with high dose MTX will be
recruited in this prospective study. Their UCP ratio will be measured before and after MTX
administration and correlated with MTX clearance. A genetic analysis will be conducted to
study the five more frequents SNPs of ABCC2 in each patient.

Inclusion Criteria


Inclusion criteria :

- Patients receiving HDMTX (≥1g/m2) for a primitive cerebral lymphoma, a large cell
lymphoma, a lymphoblastic lymphoma, a Burkitt's lymphoma or an acute lymphoblastic
leukaemia,

- over 18 years old,

- Signed informed consent.

- Affiliated to a medical assurance.

- Able to respect the protocol.

- Effective contraception for women.

Exclusion criteria :

- renal failure,

- liver failure,

- hepatic cytolysis,

- chronic respiratory deficiency,

- pregnancy,

- breast-feeding,

- Concomitant medication: phenytoin, probenecid, trimethoprim, phenylbutazone,
salicylates, non steroid anti-inflammatory, yellow fever vaccine.

- Patient included in another study in the four weeks preceding his inclusion.

Type of Study:

Observational

Study Design:

Time Perspective: Cross-Sectional

Outcome Measure:

MTX concentrations

Outcome Time Frame:

at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.

Safety Issue:

Yes

Principal Investigator

Chantal Le Guellec, PharmD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

CHRU of Tours

Authority:

France: Ministry of Health

Study ID:

P061005

NCT ID:

NCT00822432

Start Date:

October 2007

Completion Date:

August 2011

Related Keywords:

  • Central Nervous System Neoplasms
  • Lymphoma, Large B-Cell, Diffuse
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Burkitt Lymphoma
  • biomarkers
  • ABC transporters
  • MRP2
  • MTX pharmacokinetics
  • Burkitt Lymphoma
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Nervous System Neoplasms
  • Lymphoma, Large B-Cell, Diffuse
  • Central Nervous System Neoplasms

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