Ignite Creation Date:
2025-12-25 @ 3:45 AM
Ignite Modification Date:
2026-01-28 @ 6:03 PM
Study NCT ID:
NCT01987102
Status:
COMPLETED
Last Update Posted:
2020-09-25
First Post:
2013-11-05
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Investigation of [6R] 5,10-methylenetetrahydrofolate (Arfolitixorin) as Rescue Therapy for Osteosarcoma Patients Treated With HDMTX.
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012516', 'term': 'Osteosarcoma'}], 'ancestors': [{'id': 'D018213', 'term': 'Neoplasms, Bone Tissue'}, {'id': 'D009372', 'term': 'Neoplasms, Connective Tissue'}, {'id': 'D018204', 'term': 'Neoplasms, Connective and Soft Tissue'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D012509', 'term': 'Sarcoma'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D002955', 'term': 'Leucovorin'}, {'id': 'C013123', 'term': '5,10-methylenetetrahydrofolic acid'}], 'ancestors': [{'id': 'D005575', 'term': 'Formyltetrahydrofolates'}, {'id': 'D013763', 'term': 'Tetrahydrofolates'}, {'id': 'D005492', 'term': 'Folic Acid'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003067', 'term': 'Coenzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'karin.ganlov@isofolmedical.com', 'phone': '+46 (0)702433750', 'title': 'Chief Medical Officer', 'organization': 'Isofol Medical AB'}, 'certainAgreement': {'otherDetails': 'At least 30 d prior to submission the PI shall provide the Sponsor with results communication for review. The Sponsor shall notify the PI in writing about the review outcome within 30 d from receipt. No public release shall be made unless the Sponsor has consented in writing. The Sponsor may notify the PI that the material shall be withhold from submission for 90 days more to allow filing of applications to secure IPR or to take such measures to establish and preserve its proprietary rights.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '3 years, 1 month', 'description': 'The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.', 'eventGroups': [{'id': 'EG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 15mg/m2)\n\nSOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 4, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)\n\nSOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 4, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 8, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 3, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 7, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Drug clearance decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Platelet count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'White blood cell count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Left ventricular dysfunction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Localised oedema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Mucosal inflammation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 3, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 4, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 7, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Stomatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 4, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 14, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 13, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Nephropathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Muscle spasms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Bacterial disease carrier', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Cheilitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 3, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Conjunctivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}], 'seriousEvents': [{'term': 'Platelet count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 3, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Febrile neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Convulsion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Mucosal inflammation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Candida sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Neutropenic sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of AEs Per Severity (All Courses)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Grade 1', 'categories': [{'measurements': [{'value': '40', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}]}, {'title': 'Grade 2', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}]}, {'title': 'Grade 3', 'categories': [{'measurements': [{'value': '11', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'Grade 4', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total', 'description': 'Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.', 'unitOfMeasure': 'Number of AEs', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'PRIMARY', 'title': 'Number of HDMTX Related AEs Per Severity (All Courses)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Grade 1', 'categories': [{'measurements': [{'value': '25', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}]}, {'title': 'Grade 2', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}]}, {'title': 'Grade 3', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}]}, {'title': 'Grade 4', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.', 'unitOfMeasure': 'Number of AEs', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'PRIMARY', 'title': 'Number of Ongoing AEs Per HDMTX Course', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Course 1 (SOC)', 'categories': [{'measurements': [{'value': '14', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'Course 2 (SOC)', 'categories': [{'measurements': [{'value': '19', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'Course 1 (MOD)', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'Course 2 (MOD)', 'categories': [{'measurements': [{'value': '14', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.', 'unitOfMeasure': 'Number of AEs', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'PRIMARY', 'title': 'Number of Ongoing HDMTX Related AEs Per HDMTX Course', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Course 1 (SOC)', 'categories': [{'measurements': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}]}, {'title': 'Course 2 (SOC)', 'categories': [{'measurements': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}]}, {'title': 'Course 1 (MOD)', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'Course 2 (MOD)', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.', 'unitOfMeasure': 'Number of AEs', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Successful Course SOC 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course SOC 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Successful Course SOC 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Successful Course MOD 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Successful Course MOD 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 days after start of first and/or second HDMTX course in a MAP cycle', 'description': 'Definition A: Successful advancement from 1st to 2nd HDMTX course within the same MAP cycle. Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:\n\n1. Serum MTX: ≤0.1μmol/L\n2. Neutrophils: ≥0.25x109/L\n3. Platelets: ≥50x109/L\n4. Serum bilirubin: ≤1.25 x upper limit of normal (ULN)\n5. Glomerular filtration rate (GFR) ≥70 mL/min/1.73m2\n6. No AE Grade 2 or more related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator\n\nDefinition B: Successful advancement to next MAP cycle\n\nFulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:\n\n1. Serum MTX: ≤0.1μmol/L\n2. Neutrophils: ≥ 0.75 x 109/L\n3. Platelets: ≥75x109/L\n4. Serum bilirubin: ≤1.25xULN\n5. GFR ≥70 mL/min/1.73m2\n6. No AE Grade 2 or more related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Successful Course SOC 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course SOC 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Successful Course MOD 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 days after start of first HDMTX course in a MAP cycle', 'description': 'Definition A: Successful advancement from first to second HDMTX course within the same MAP cycle\n\nFulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:\n\n1. Serum MTX: ≤ 0.1 μmol/L\n2. Neutrophils: ≥ 0.25 x 109/L\n3. Platelets: ≥ 50 x 109/L\n4. Serum bilirubin: ≤ 1.25 x ULN\n5. GFR ≥ 70 mL/min/1.73 m2\n6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Successful Course SOC 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Successful Course MOD 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Unsuccessful Course MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 days after start of second HDMTX course in a MAP cycle', 'description': 'Definition B: Successful advancement to next MAP cycle\n\nFulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:\n\n1. Serum MTX: ≤ 0.1 μmol/L\n2. Neutrophils: ≥ 0.75 x 109/L\n3. Platelets: ≥ 75 x 109/L\n4. Serum bilirubin: ≤ 1.25 x ULN\n5. GFR ≥ 70 mL/min/1.73 m2\n6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Time to Successful MTX Elimination (Definition C)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Time (h) Course SOC 1', 'categories': [{'measurements': [{'value': '84.52', 'spread': '15.00', 'groupId': 'OG000'}, {'value': '62.75', 'spread': '3.21', 'groupId': 'OG001'}]}]}, {'title': 'Time (h) Course SOC 2', 'categories': [{'measurements': [{'value': '77.0', 'spread': '19.60', 'groupId': 'OG000'}, {'value': '62.75', 'spread': '9.91', 'groupId': 'OG001'}]}]}, {'title': 'Time (h) Course MOD 1', 'categories': [{'measurements': [{'value': '74.00', 'spread': '15.87', 'groupId': 'OG000'}, {'value': '65.75', 'spread': '11.50', 'groupId': 'OG001'}]}]}, {'title': 'Time (h) Course MOD 2', 'categories': [{'measurements': [{'value': '72.50', 'spread': '15.78', 'groupId': 'OG000'}, {'value': '88.0', 'spread': '43.41', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition C: Time to successful MTX elimination = Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'unitOfMeasure': 'hours', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of HDMTX Courses in Which the Initial Hydration Was Increased', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Hydration change in Course SOC 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Unchanged hydration Course SOC 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Hydration change in Course SOC 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Unchanged hydration Course SOC 2', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Hydration change in Course MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Unchanged hydration Course MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Hydration change in course MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Unchanged hydration Course MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'unitOfMeasure': 'HDMTX courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of HDMTX Courses With Delayed MTX Elimination (Definition D).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Delayed MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Delayed MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Delayed MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Delayed MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition D: Delayed MTX elimination (according to COGs excretion toxicity management instructions)\n\nS-MTX levels of:\n\n\\> 10 μmol/L at 24 h after start of MTX administration, OR \\> 1 μmol/L at 48 h after start of MTX administration, OR \\> 0.1 μmol/L at 72 h after start of MTX administration or later', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Delayed early MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed early MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Delayed early MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed early MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Delayed early MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed early MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Delayed early MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed early MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition E: Delayed early MTX elimination (according to US label for Calcium Folinate)\n\nS-MTX levels of:\n\n* 50 μmol/L at 24 hours after start of MTX administration, OR\n* 5 μmol/L at 48 hours after start of MTX administration OR An increase in S-Creatinine level of 100% or greater at 24 hours after start of MTX administration.', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Delayed late MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed late MTX elimination in Course SOC 1', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Delayed late MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed late MTX elimination in Course SOC 2', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Delayed late MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed late MTX elimination in Course MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Delayed late MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Undelayed late MTX elimination in Course MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition F: Delayed late MTX elimination (according to US label for Calcium Folinate)\n\nS-MTX level:\n\n\\> 0.2 μmol/L at 72 hours AND \\> 0.1 μmol/L at 96 hours after start of MTX administration.', 'unitOfMeasure': 'Number of courses', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Grade A2 (24h) SOC 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (24h) SOC 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (24h) MOD 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (24h) MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (24h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (24h) SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (24h) MOD 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (24h) MOD 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'None (24h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'None (24h) SOC 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'None (24h) MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'None (24h) MOD 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (48h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (48h) SOC 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (48h) MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (48h) MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (48h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (48h) SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (48h) MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (48h) MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'None (48h) SOC 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'None (48h) SOC 2', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'None (48h) MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'None (48h) MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade A1 (72h) SOC 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade A1 (72h) SOC 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade A1 (72h) MOD 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Grade A1 (72h) MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (72h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (72h) SOC 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (72h) MOD 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade A2 (72h) MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (72h) SOC 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (72h) SOC 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (72h) MOD 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Grade B (72h) MOD 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'None (72h) SOC 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'None (72h) SOC 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'None (72h) MOD 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'None (72h) MOD 2', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': "The MTX-toxicity management instructions provided in the protocol are based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331, EURAMOS 1. The COG recommend changes in the hydration and the rescue frequency and/or dose to be done if pre-specified toxicities of different severity grades occur.", 'unitOfMeasure': 'Number of MTX excretion toxicities', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}, {'type': 'SECONDARY', 'title': 'Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'OG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'classes': [{'title': 'Grade 1 (ALL AEs)', 'categories': [{'measurements': [{'value': '40', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}]}, {'title': 'Grade 2 (ALL AEs)', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}]}, {'title': 'Grade 3 (ALL AEs)', 'categories': [{'measurements': [{'value': '11', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'Grade 4 (ALL AEs)', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}]}]}, {'title': 'Any Grade (ALL AEs)', 'categories': [{'measurements': [{'value': '62', 'groupId': 'OG000'}, {'value': '49', 'groupId': 'OG001'}]}]}, {'title': 'Grade 1 (AEs Related to MTX)', 'categories': [{'measurements': [{'value': '25', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}]}, {'title': 'Grade 2 (AEs Related to MTX)', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}]}, {'title': 'Grade 3 (AEs Related to MTX)', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}]}, {'title': 'Grade 4 (AEs Related to MTX)', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Any Grade (AEs Related to MTX)', 'categories': [{'measurements': [{'value': '38', 'groupId': 'OG000'}, {'value': '38', 'groupId': 'OG001'}]}]}, {'title': 'ALAT increase (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ALAT increase (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'ALAT increase (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ALAT increase (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ALAT increase (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Anemia (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Anemia (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Anemia (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Anemia (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Anemia (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ASAT increased (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'ASAT increased (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ASAT increased (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ASAT increased (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'ASAT increased (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Cheilitis (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Cheilitis (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Cheilitis (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Cheilitis (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Cheilitis (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Convulsion (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Convulsion (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Convulsion (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Convulsion (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Convulsion (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Diarrhoea (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Diarrhoea (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Diarrhoea (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Diarrhoea (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Diarrhoea (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Drug clearance decreased (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Drug clearance decreased (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Drug clearance decreased (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Drug clearance decreased (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Drug clearance decreased (Related to MTX) AnyGrade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Febrile neutropenia (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Febrile neutropenia (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Febrile neutropenia (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Febrile neutropenia (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Febrile neutropenia (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Headache (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Headache (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Headache (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Headache (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Headache (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Nausea (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Nausea (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Nausea (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Nausea (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Nausea (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'Nephropathy (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Nephropathy (Related to MTX) Grade 21', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Nephropathy (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Nephropathy (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Nephropathy (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Neutropenia (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutropenia (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutropenia (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutropenia (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Neutropenia (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Neutrophil count decrease (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutrophil count decrease (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutrophil count decrease (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Neutrophil count decrease (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Neutrophil count decrease (Related to MTX)AnyGrade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Pyrexia (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Pyrexia (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Pyrexia (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Pyrexia (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Pyrexia (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Stomatitis (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Stomatitis (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Stomatitis (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Stomatitis (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Stomatitis (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'Vomiting (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}]}, {'title': 'Vomiting (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Vomiting (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Vomiting (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Vomiting (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'WBC count decreased (Related to MTX) Grade 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'WBC count decreased (Related to MTX) Grade 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'WBC count decreased (Related to MTX) Grade 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'WBC count decreased (Related to MTX) Grade 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'WBC count decreased (Related to MTX) Any Grade', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for all 4 courses of HDMTX in total', 'description': 'The severity of AEs have been done using NCI CTCAE v4.0. Total number of AEs per severity grade are presented for all AEs and for AEs related to MTX. For AEs related to MTX the number of AEs occurring per preferred term and severity grade are detailed.The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.', 'unitOfMeasure': 'Number of AEs', 'reportingStatus': 'POSTED', 'populationDescription': 'The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'FG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}], 'periods': [{'title': '2 Courses of HDMTX With SOC Rescue', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Laboratory abnormality', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Change in planned chemotherapy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Incorrectly included', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}, {'title': '2 Courses of HDMTX With MOD Rescue', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Patients were pre-screened for eligibility to participate by the principal investigator among those patients who have received confirmed diagnosis of osteosarcoma and were planned for surgical resection of their tumor in combination with neoadjuvant or adjuvant chemotherapy.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'BG001', 'title': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)\n\nTreatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Sweden', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Hungary', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}, {'title': 'Czechia', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}]}, {'title': 'Poland', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-09', 'completionDateStruct': {'date': '2017-01-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-09-07', 'studyFirstSubmitDate': '2013-11-05', 'resultsFirstSubmitDate': '2018-11-14', 'studyFirstSubmitQcDate': '2013-11-12', 'lastUpdatePostDateStruct': {'date': '2020-09-25', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-04-01', 'studyFirstPostDateStruct': {'date': '2013-11-19', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-06-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-01-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of AEs Per Severity (All Courses)', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total', 'description': 'Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.'}, {'measure': 'Number of HDMTX Related AEs Per Severity (All Courses)', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.'}, {'measure': 'Number of Ongoing AEs Per HDMTX Course', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.'}, {'measure': 'Number of Ongoing HDMTX Related AEs Per HDMTX Course', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for each course of HDMTX', 'description': 'Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.'}], 'secondaryOutcomes': [{'measure': 'Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B', 'timeFrame': '8 days after start of first and/or second HDMTX course in a MAP cycle', 'description': 'Definition A: Successful advancement from 1st to 2nd HDMTX course within the same MAP cycle. Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:\n\n1. Serum MTX: ≤0.1μmol/L\n2. Neutrophils: ≥0.25x109/L\n3. Platelets: ≥50x109/L\n4. Serum bilirubin: ≤1.25 x upper limit of normal (ULN)\n5. Glomerular filtration rate (GFR) ≥70 mL/min/1.73m2\n6. No AE Grade 2 or more related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator\n\nDefinition B: Successful advancement to next MAP cycle\n\nFulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:\n\n1. Serum MTX: ≤0.1μmol/L\n2. Neutrophils: ≥ 0.75 x 109/L\n3. Platelets: ≥75x109/L\n4. Serum bilirubin: ≤1.25xULN\n5. GFR ≥70 mL/min/1.73m2\n6. No AE Grade 2 or more related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator'}, {'measure': 'Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.', 'timeFrame': '8 days after start of first HDMTX course in a MAP cycle', 'description': 'Definition A: Successful advancement from first to second HDMTX course within the same MAP cycle\n\nFulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle:\n\n1. Serum MTX: ≤ 0.1 μmol/L\n2. Neutrophils: ≥ 0.25 x 109/L\n3. Platelets: ≥ 50 x 109/L\n4. Serum bilirubin: ≤ 1.25 x ULN\n5. GFR ≥ 70 mL/min/1.73 m2\n6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator'}, {'measure': 'Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.', 'timeFrame': '8 days after start of second HDMTX course in a MAP cycle', 'description': 'Definition B: Successful advancement to next MAP cycle\n\nFulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle:\n\n1. Serum MTX: ≤ 0.1 μmol/L\n2. Neutrophils: ≥ 0.75 x 109/L\n3. Platelets: ≥ 75 x 109/L\n4. Serum bilirubin: ≤ 1.25 x ULN\n5. GFR ≥ 70 mL/min/1.73 m2\n6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator'}, {'measure': 'Time to Successful MTX Elimination (Definition C)', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition C: Time to successful MTX elimination = Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L'}, {'measure': 'Number of HDMTX Courses in Which the Initial Hydration Was Increased', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L'}, {'measure': 'Number of HDMTX Courses With Delayed MTX Elimination (Definition D).', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition D: Delayed MTX elimination (according to COGs excretion toxicity management instructions)\n\nS-MTX levels of:\n\n\\> 10 μmol/L at 24 h after start of MTX administration, OR \\> 1 μmol/L at 48 h after start of MTX administration, OR \\> 0.1 μmol/L at 72 h after start of MTX administration or later'}, {'measure': 'Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition E: Delayed early MTX elimination (according to US label for Calcium Folinate)\n\nS-MTX levels of:\n\n* 50 μmol/L at 24 hours after start of MTX administration, OR\n* 5 μmol/L at 48 hours after start of MTX administration OR An increase in S-Creatinine level of 100% or greater at 24 hours after start of MTX administration.'}, {'measure': 'Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': 'Definition F: Delayed late MTX elimination (according to US label for Calcium Folinate)\n\nS-MTX level:\n\n\\> 0.2 μmol/L at 72 hours AND \\> 0.1 μmol/L at 96 hours after start of MTX administration.'}, {'measure': 'Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions', 'timeFrame': 'Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L', 'description': "The MTX-toxicity management instructions provided in the protocol are based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331, EURAMOS 1. The COG recommend changes in the hydration and the rescue frequency and/or dose to be done if pre-specified toxicities of different severity grades occur."}, {'measure': 'Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.', 'timeFrame': 'From the start of HDMTX administration through 8 days post dose for all 4 courses of HDMTX in total', 'description': 'The severity of AEs have been done using NCI CTCAE v4.0. Total number of AEs per severity grade are presented for all AEs and for AEs related to MTX. For AEs related to MTX the number of AEs occurring per preferred term and severity grade are detailed.The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Methotrexate', 'Rescue treatment'], 'conditions': ['Osteosarcoma']}, 'descriptionModule': {'briefSummary': 'An open-label, multicenter, phase I/II clinical trial to identify the \\[6R\\] 5,10-methylenetetrahydrofolate (arfolitixorin) dose with most favorable safety prospect and confirmed ability to mitigate high-dose methotrexate induced toxicity during treatment of osteosarcoma patients', 'detailedDescription': "This is a non-blinded, multicenter, exploratory study in osteosarcoma patients. The study focuses on the overall safety of the HDMTX courses given within a Methotrexate, Adriamycin (doxorubin) and cisPlatin (MAP) treatment schedule, which is closely related to the efficacy of the concomitantly administered folate rescue treatment. Additionally the study aimes to collect pharmacokinetic (PK) profiles of metotrexate (MTX) in serum, of folate metabolites in plasma and to decide the Modufolin® dose to use in future studies.\n\nPatients are enrolled in the study at the first, third or the fifth HDMTX course in a MAP treatment schedule and receive folate rescue therapy according to a strategy based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331.\n\nFolate rescue treatment with Calcium Folinate (SOC) or Modufolin® (MOD) commence 24 h after start of HDMTX administration and then every 6 h until the serum MTX levels are ≤0.1 μmol/L. In case delayed MTX elimination occurs with significant increase in S-creatinine and/or occurrence of oral mucositis or signs of hypo cellular bone marrow, the folate rescue dose and/or the administered hydration will be adjusted in accordance with the COG based MTX toxicity management recommendations.\n\nAll patients receives SOC (15 mg/m2) in the first 2 HDMTX courses and MOD in the following 2 courses. Patients are enrolled in one of two MOD dose cohorts: Cohort 1 (15 mg/m2) and Cohort 2 (30 or 7.5 mg/m2 depending on outcome of Cohort 1). Only patients with successful advancements from the first 2 HDMTX courses with Calcium Folinate are allowed to continue with MOD as rescue in the following MAP cycle.\n\nSafety data will be reviewed by an independent board, Data and Safety Monitoring Board (DSMB) that will assess each patient and made recommendations regarding the enrolment of subsequent patients. Furthermore, the DSMB will make a dose level recommendation for Cohort 2 and also a recommendation whether younger children may be allowed in this cohort."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '40 Years', 'minimumAge': '6 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Main Inclusion Criteria (HDMTX with SOC rescue):\n\n* Patients must have histological evidence of osteosarcoma (metastatic disease accepted).\n* Patients must be eligible for HDMTX according to the MAP treatment schedule described in the study protocol and fulfill all of the criteria below prior to first course of HDMTX in the study.\n\n 1. Serum MTX: ≤0.1μmol/L\n 2. Neutrophils: ≥0.25x109/L\n 3. Platelets: ≥50x109/L\n 4. Serum bilirubin: ≤1.25x upper limit of normal (ULN)\n 5. Glomerular filtration rate (GFR) ≥70 mL/min/1.73m2\n 6. No adverse event (AE) Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator.\n* Patients must be 12-40 years of age. This age range may be extended with younger patients for enrolment in Cohort 2 if collected data from Cohort 1 support this and it is recommended by the DSMB.\n\nExclusion criteria for enrolment:\n\n* Involvement in another clinical trial within 30 days before enrolment in the study.\n* Hypersensitivity to Calcium Folinate.\n* Previous treatment with glucarpidase.\n* Known serious concomitant systemic disorders (e.g., active infection including HIV, liver dysfunction, cardiac disease) that, in the opinion of the investigator, would compromise the patient's ability to complete the study\n\nMain Inclusion criteria for continuation (HDMTX treatment with Modufolin rescue):\n\n* Patients, who were included in the study in accordance with the inclusion criteria above, must have received 2 adjacent courses of HDMTX with SOC rescue according to the MAP treatment schedule in accordance with this study protocol.\n* Patients eligible for continued HDMTX according to the MAP treatment schedule and with a history of successful advancement from first to second HDMTX course within the previous MAP cycle\n* Patients eligible for continued HDMTX according to the MAP treatment schedule and with a history of successful advancement to next MAP cycle after end of previous MAP cycle\n* No significant changes to the patient's medical condition from the start of the study that in the opinion of the investigator would compromise the patient's ability to complete the study.\n* Patients who have undergone surgical resection of their tumor must have recovered from their surgery and be eligible to continue on the MAP regimen; any post-operative complications should be resolved to NCI CTCAE v4.0 Grade 1 or better."}, 'identificationModule': {'nctId': 'NCT01987102', 'briefTitle': 'Investigation of [6R] 5,10-methylenetetrahydrofolate (Arfolitixorin) as Rescue Therapy for Osteosarcoma Patients Treated With HDMTX.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Isofol Medical AB'}, 'officialTitle': 'An Open-Label, Multicenter, Phase I/II Clinical Trial to Identify the Modufolin® Dose With Most Favorable Safety Prospect and Confirmed Ability to Mitigate High-Dose Methotrexate Induced Toxicity During Treatment of Osteosarcoma Patients', 'orgStudyIdInfo': {'id': 'ISO-MTX-003'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1', 'description': '1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX Courses using \\[6R\\] 5,10-methylenetetrahydrofolate rescue 15mg/m2)', 'interventionNames': ['Drug: Calcium Folinate', 'Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2', 'description': '1 MAP cycle (incl. 2 HDMTX Courses using Calcium Folinate rescue 15mg/m2)\n\n1 MAP cycle (incl. 2 HDMTX Courses using \\[6R\\] 5,10-methylenetetrahydrofolate rescue 7,5mg/m2 or 30mg/m2\\*)\n\n\\*Dose will depend on outcome from Cohort 1', 'interventionNames': ['Drug: Calcium Folinate', 'Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)']}], 'interventions': [{'name': 'Calcium Folinate', 'type': 'DRUG', 'otherNames': ['Leucovorin'], 'description': 'The enrolled patients will be treated according to the MAP schedule and will receive the study drug Calcium Folinate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations.\n\nAll patients will receive standard o care (SOC) in the two (2) first HDMTX courses and \\[6R\\] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) \\[6R\\] 5,10-methylenetetrahydrofolate dose cohort groups: with \\[6R\\] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort.', 'armGroupLabels': ['Cohort 1', 'Cohort 2']}, {'name': '[6R] 5,10-methylenetetrahydrofolate (arfolitixorin)', 'type': 'DRUG', 'otherNames': ['Modufolin', 'arfolitixorin'], 'description': 'The enrolled patients will be treated according to the MAP schedule and will receive the study drug \\[6R\\] 5,10-methylenetetrahydrofolate commencing 24 hours after the administration of HDMTX and then every 6 hours (q6h) thereafter until the S-MTX levels are ≤ 0.1 µmol/L, in accordance with COG management recommendations.\n\nAll patients will receive standard o care (SOC) in the two (2) first HDMTX courses and \\[6R\\] 5,10-methylenetetrahydrofolate in the two (2) following courses. Patients will be enrolled in two (2) \\[6R\\] 5,10-methylenetetrahydrofolate® dose cohort groups: with \\[6R\\] 5,10-methylenetetrahydrofolate start dose of 15 mg/m2 (i.e. the same as for SOC rescue) the first cohort will be administered, and 7.5 or 30 mg/m2 in the second cohort.', 'armGroupLabels': ['Cohort 1', 'Cohort 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '62500', 'city': 'Brno', 'country': 'Czechia', 'facility': 'Fakultní nemocnice Brno Klinika detske onkologie', 'geoPoint': {'lat': 49.19522, 'lon': 16.60796}}, {'zip': '15006', 'city': 'Prague', 'country': 'Czechia', 'facility': 'Fakultní nemocnice v Motole', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}, {'zip': '1094', 'city': 'Budapest', 'country': 'Hungary', 'facility': 'Semmelweis Egyetem II. Sz. Gyermekgyógyászati Klinika', 'geoPoint': {'lat': 47.49835, 'lon': 19.04045}}, {'zip': '01-211', 'city': 'Warsaw', 'country': 'Poland', 'facility': 'Instytut Matki i Dziecka', 'geoPoint': {'lat': 52.22977, 'lon': 21.01178}}, {'zip': '22185', 'city': 'Lund', 'country': 'Sweden', 'facility': 'Department of Oncology, Skåne University Hospital', 'geoPoint': {'lat': 55.70584, 'lon': 13.19321}}], 'overallOfficials': [{'name': 'Mikael Eriksson, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Oncology, Skåne University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Isofol Medical AB', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}