NCT00822432

Brief Summary

High dose methotrexate (MTX) is responsible of severe toxicity in patients in whom elimination from plasma is delayed. Factors responsible for MTX accumulation are partly known but some patients still experience toxicity despite adequate measures being taken. Our hypothesis is that renal tubular secretion may be impaired in these patients. This study aims at evaluating the performance of the UCP ratio (urinary ratio of coproporphyrins), a putative biomarker of tubular secretion, in predicting delayed MTX elimination.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
85

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Oct 2007

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2007

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

January 13, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2009

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2011

Completed
Last Updated

July 31, 2012

Status Verified

January 1, 2009

Enrollment Period

3.8 years

First QC Date

January 13, 2009

Last Update Submit

July 30, 2012

Conditions

Central Nervous System NeoplasmsLymphoma, Large B-Cell, DiffusePrecursor B-Cell Lymphoblastic Leukemia-LymphomaBurkitt Lymphoma

Keywords

biomarkersABC transportersMRP2MTX pharmacokinetics

Outcome Measures

Primary Outcomes (1)

  • MTX concentrations

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

Secondary Outcomes (4)

  • The UCP I/(I+III) ratio

    before and at the end of MTX infusion and at the end of hospitalisation.

  • Five polymorphisms of the ABCC2 gene (-24C/T, 1249G/A, 3563T/A, 4544G/A)

    during the study

  • Blood cells count .

    before MTX infusion and at the end of hospitalisation

  • Renal function

    before MTX infusion and at the end of hospitalisation

Study Arms (1)

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

* Patients aged more than 18 y, hospitalized in the neurology or in the haematology department at PSP hospital of Paris or in the haematology department at CHU of Tours * Who should receive high-dose methotrexate (\> 1 g/m2) for one of the following conditions : Central Nervous System Neoplasms; Lymphoma, Large B-Cell, Diffuse; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma or Burkitt lymphoma

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

University Hospital Centre of Tours

Tours, 37000, France

Location

Related Publications (1)

  • Benz-de Bretagne I, Zahr N, Le Gouge A, Hulot JS, Houillier C, Hoang-Xuan K, Gyan E, Lissandre S, Choquet S, Le Guellec C. Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance. Br J Clin Pharmacol. 2014 Aug;78(2):329-42. doi: 10.1111/bcp.12326.

    PMID: 24433481DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood

MeSH Terms

Conditions

Central Nervous System NeoplasmsLymphoma, Large B-Cell, DiffusePrecursor B-Cell Lymphoblastic Leukemia-LymphomaBurkitt Lymphoma

Condition Hierarchy (Ancestors)

Nervous System NeoplasmsNeoplasms by SiteNeoplasmsNervous System DiseasesLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, LymphoidLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus Infections

Study Officials

  • Chantal Le Guellec, PharmD, PhD

    CHRU of Tours

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2009

First Posted

January 14, 2009

Study Start

October 1, 2007

Primary Completion

August 1, 2011

Study Completion

August 1, 2011

Last Updated

July 31, 2012

Record last verified: 2009-01

Locations

FR(2)