- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01678508
Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia
September 4, 2012 updated by: Kjeld Schmiegelow, Rigshospitalet, Denmark
Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia - Influence on Cure Rates and Risk of Second Cancer
In a population-based study to explore the impact of TPMT-status on the risk of relapse and of second cancer among all patients treated according to the NOPHO ALL2000.
Study Overview
Status
Completed
Conditions
Detailed Description
The thiopurines 6-mercaptopurine (6MP) and 6-thioguanine (6TG) are widely used in the treatment of childhood acute lymphoblastic leukemia (ALL).
They primarily exert their cytotoxicity through conversion into 6-thioguanine nucleotides (6TGN) that are incorporated into DNA.
Interindividual variations in response to thiopurine therapy are influenced by genetically determined polymorphisms in the activity of the enzyme thiopurine methyltransferase (TPMT).
TPMT competes with the formation of 6TGN, as it methylates the thiopurines (especially 6MP) and some of their metabolites.
Approximately ten percent of all individuals are TPMT heterozygous, with one wild type and one low activity allele, and one in three hundred individuals are TPMT deficient with two low activity alleles.
During the maintenance therapy phase of the treatment of childhood ALL, which may last several years, 6MP is given on a daily basis at a starting dose of 75 mg/m.sq./day, which is subsequently adjusted to a white blood cell count of 1.5-3.5 x109/L.
We have previously demonstrated that the risk of relapse is reduced by more than 50%, but the risk of second cancer was increased 3-fold among TPMT low activity patients.
Accordingly, the Nordic ALL2000 protocol recommended the dosing of 6MP to be based on the patients TPMT activity.
In the present study of almost 1000 Nordic patients, we will explore whether this strategy of TPMT-based individualised 6MP dosing have benefitted the patients by reducing their risk of second cancer while preserving their low risk of relapse.
Study Type
Observational
Enrollment (Actual)
1020
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Copenhagen, Denmark, 2100
- Rigshospitalet
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 15 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
The study cohort is based on patients enrolled in the NOPHO ALL2000 protocol.
Description
Inclusion Criteria:
- included in the NOPHO ALL2000 protocol
- entered 6-mercaptopurine/Methotrexate maintenance therapy in first remission
- available TPMT phenotype and/or genotype
Exclusion Criteria:
- children with Down Syndrome
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Retrospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative risk of relapse and risk of second cancer by Kaplan-Meier analysis with Gray's test comparisons at 10 years
Time Frame: Up to 10 years from diagnosis
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The risks will be reported as percentages.
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Up to 10 years from diagnosis
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Kjeld Schmiegelow, M.D., Rigshospitalet, Denmark
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2002
Primary Completion (Actual)
July 1, 2011
Study Completion (Actual)
February 1, 2012
Study Registration Dates
First Submitted
May 22, 2012
First Submitted That Met QC Criteria
September 4, 2012
First Posted (Estimate)
September 5, 2012
Study Record Updates
Last Update Posted (Estimate)
September 5, 2012
Last Update Submitted That Met QC Criteria
September 4, 2012
Last Verified
September 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NOPHO ALL2000 TPMT and outcome
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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