Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia
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| First Received Date ICMJE | May 22, 2012 | ||||
| Last Updated Date | September 4, 2012 | ||||
| Start Date ICMJE | January 2002 | ||||
| Primary Completion Date | July 2011 (final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
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. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | Complete list of historical versions of study NCT01678508 on ClinicalTrials.gov Archive Site | ||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia | ||||
| Official Title ICMJE | Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia - Influence on Cure Rates and Risk of Second Cancer | ||||
| Brief Summary | 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. |
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| 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. |
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| Study Type ICMJE | Observational | ||||
| Study Design ICMJE | Observational Model: Cohort Time Perspective: Retrospective |
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| Target Follow-Up Duration | Not Provided | ||||
| Biospecimen | Retention: Samples With DNA Description: whole blood stored for a subset of patients |
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| Sampling Method | Probability Sample | ||||
| Study Population | The study cohort is based on patients enrolled in the NOPHO ALL2000 protocol. |
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| Condition ICMJE | Acute Lymphoblastic Leukemia | ||||
| Intervention ICMJE | Not Provided | ||||
| Study Group/Cohort (s) | Not Provided | ||||
| Publications * | 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. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Enrollment ICMJE | 1020 | ||||
| Completion Date | February 2012 | ||||
| Primary Completion Date | July 2011 (final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Gender | Both | ||||
| Ages | 1 Year to 15 Years | ||||
| Accepts Healthy Volunteers | No | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Location Countries ICMJE | Denmark | ||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT01678508 | ||||
| Other Study ID Numbers ICMJE | NOPHO ALL2000 TPMT and outcome | ||||
| Has Data Monitoring Committee | No | ||||
| Responsible Party | Kjeld Schmiegelow, Rigshospitalet, Denmark | ||||
| Study Sponsor ICMJE | Rigshospitalet, Denmark | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| Information Provided By | Rigshospitalet, Denmark | ||||
| Verification Date | September 2012 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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