Ignite Creation Date:
2025-12-24 @ 11:45 PM
Ignite Modification Date:
2026-03-01 @ 5:39 PM
Study NCT ID:
NCT01886651
Status:
COMPLETED
Last Update Posted:
2013-06-26
First Post:
2013-06-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Influence of Thiopurine Methyltransferase Activity on Toxicity After High-dose Methotrexate in Childhood Acute Lymphoblastic Leukemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054198', 'term': 'Precursor Cell Lymphoblastic Leukemia-Lymphoma'}], 'ancestors': [{'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'whole blood stored for a subset of patients'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 411}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-06', 'completionDateStruct': {'date': '2012-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-06-21', 'studyFirstSubmitDate': '2013-06-21', 'studyFirstSubmitQcDate': '2013-06-21', 'lastUpdatePostDateStruct': {'date': '2013-06-26', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-06-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Toxicity of treatment, degree of myelo- and hepatotoxicity', 'timeFrame': '7-28 days after high-dose methotrexate'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['acute lymphoblastic leukemia', 'child', '6-mercaptopurine', 'methotrexate'], 'conditions': ['Acute Lymphoblastic Leukemia']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to explore the impact of thiopurine methyltransferase (TPMT) activity on the risk of HDM-related bone marrow- and hepatotoxicity and treatment interruptions during maintenance therapy for children with ALL.\n\nHypothesis of the study: Patients with TPMT activity compatible with TPMT low activity polymorphisms have an increased risk of toxicity following high-dose methotrexate (HDM) compared to children with normal TPMT activity.', 'detailedDescription': 'High-dose methotrexate (HDM) given concurrently with oral 6-mercaptopurine (6MP) may be followed by myelotoxicity, which may necessitate treatment interruption and thus interfere with the efficacy of the treatment of childhood ALL. Several studies have indicated that MTX and 6MP act synergistically. It has previously been reported that the risk of significant bone-marrow suppression is increased if oral 6MP is coadministered with HDM during maintenance therapy and that reductions of the dose of concurrently given oral 6MP can reduce the risk of significant myelotoxicity following HDM. MTX may increase the bioavailability of 6MP through inhibition of xanthine oxidase, which catabolizes 6MP. In addition, MTX may through inhibition of de novo purine synthesis enhance the availability of 6-thioguanine nucleotides (6TGN) that primarily exert the cytotoxic effect of 6MP.\n\nThe enzyme TPMT competes with the formation of 6TGN, as it methylates 6MP and thus create relatively non-toxic metabolites. TPMT heterozygous patients with one wild type and one low-activity allele have a higher risk of myelosuppression and treatment interruption compared to patients with TPMT wild type. Furthermore, TPMT heterozygous patients have a reduced risk of relapse and a higher risk of secondary malignancy compared to patients with TPMT wild type.\n\nLittle has been published on the influence of both TPMT activity and 6MP dosage on myelo- and hepatotoxicity following HDM.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '15 Years', 'minimumAge': '1 Year', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'The study cohort was based on patients enrolled in the NOPHO ALL92 protocol, where 97% of all eligible patients were included.\n\nParticipation in this study was on the basis of TPMT status that was randomly missing.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* included in the NOPHO ALL92 protocol\n* available TPMT phenotype\n* treated at least once with HD-MTX 5.0 g/m2 (+- 10%) during maintenance therapy\n* at least one available measurement on blood counts or alanine aminotransferase levels 28 days after HD-MTX\n\nExclusion Criteria:\n\n* HR ALL\n* children with Down Syndrome\n* Events during maintenance therapy\n* TPMT deficiency'}, 'identificationModule': {'nctId': 'NCT01886651', 'briefTitle': 'The Influence of Thiopurine Methyltransferase Activity on Toxicity After High-dose Methotrexate in Childhood Acute Lymphoblastic Leukemia', 'organization': {'class': 'OTHER', 'fullName': 'Rigshospitalet, Denmark'}, 'officialTitle': 'The Influence of Thiopurine Methyltransferase Activity on Bone Marrow- and Hepato-toxicity After High-dose Methotrexate in Childhood Acute Lymphoblastic Leukemia', 'orgStudyIdInfo': {'id': 'NOPHO ALL92 study HDM TPMT'}}, 'contactsLocationsModule': {'locations': [{'zip': '2100', 'city': 'Copenhagen', 'country': 'Denmark', 'facility': 'Kjeld Schmiegelow', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}], 'overallOfficials': [{'name': 'Kjeld Schmiegelow, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rigshospitalet, Denmark'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rigshospitalet, Denmark', 'class': 'OTHER'}, 'collaborators': [{'name': 'Nordic Society for Pediatric Hematology and Oncology', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Kjeld Schmiegelow', 'investigatorAffiliation': 'Rigshospitalet, Denmark'}}}}