Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kjeld Schmiegelow, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01678508
First received: May 22, 2012
Last updated: September 4, 2012
Last verified: September 2012

May 22, 2012
September 4, 2012
January 2002
July 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
The risks will be reported as percentages.
Same as current
Complete list of historical versions of study NCT01678508 on ClinicalTrials.gov Archive Site
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Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia
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.

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.

Observational
Observational Model: Cohort
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:

whole blood stored for a subset of patients

Probability Sample

The study cohort is based on patients enrolled in the NOPHO ALL2000 protocol.

Acute Lymphoblastic Leukemia
Not Provided
Not Provided
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1020
February 2012
July 2011   (final data collection date for primary outcome measure)

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
Both
1 Year to 15 Years
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT01678508
NOPHO ALL2000 TPMT and outcome
No
Kjeld Schmiegelow, Rigshospitalet, Denmark
Rigshospitalet, Denmark
Not Provided
Principal Investigator: Kjeld Schmiegelow, M.D. Rigshospitalet, Denmark
Rigshospitalet, Denmark
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP