Central Nervous System NeoplasmsCOMETHNCT00822432
Coproporphyrine Isomers and Methotrexate Elimination
An observational study of Central Nervous System Neoplasms and Lymphoma, Large B-Cell, Diffuse, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Neoplasms, Lymphoma, Large B-Cell, Diffuse, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
- How many people
- 85 participants
- Where
- 2 sitesFrance
- Study dates
- Oct 2007to Aug 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Pitié-Salpêtrière Hospital
Paris, 75013
University Hospital Centre of Tours
Tours, 37000
About this study
Official title: Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy
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.
Read the detailed description
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.
- Conditions
- Central Nervous System Neoplasms, Lymphoma, Large B-Cell, Diffuse, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
- Keywords
- biomarkers, ABC transporters, MRP2, MTX pharmacokinetics
- Medical subject headings
- Central Nervous System Neoplasms, Lymphoma, Large B-Cell, Diffuse, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTX concentrations
Measured: at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.
Secondary outcomes (4)
The UCP I/(I+III) ratio
Measured: 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)
Measured: during the study
Blood cells count .
Measured: before MTX infusion and at the end of hospitalisation
Renal function
Measured: before MTX infusion and at the end of hospitalisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2009 (estimated)
- Study startOct 2007
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Central Nervous System NeoplasmsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Cross-sectional
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chantal Le Guellec, PharmD, PhD, Principal investigator, CHRU of Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00822432
- Sponsor's protocol ID
- P061005
- Acronym
- COMETH
- Status last verified
- Jan 2009
- First submitted
- 13 Jan 2009
- Last updated
- 31 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24433481
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy
- ClinicalTrials.gov ID
- NCT00822432
- Acronym / sponsor ID
- COMETH / P061005
- Conditions
- Central Nervous System Neoplasms, Lymphoma, Large B-Cell, Diffuse, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
- Keywords
- biomarkers, ABC transporters, MRP2, MTX pharmacokinetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 14 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- renal failure,
- liver failure,
- hepatic cytolysis,
- chronic respiratory deficiency,
- pregnancy,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MTX concentrations
Time frame: at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.
4 secondary outcomes
The UCP I/(I+III) ratio
Time frame: 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)
Time frame: during the study
Blood cells count .
Time frame: before MTX infusion and at the end of hospitalisation
Renal function
Time frame: before MTX infusion and at the end of hospitalisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2012.
- Derived from this study: PubMed 24433481Benz-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chantal Le Guellec, PharmD, PhD principal investigator
CHRU of Tours
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Central Nervous System Neoplasms and Lymphoma, Large B-Cell, Diffuse, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTX concentrations (time frame: at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00822432, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2012.