Ignite Creation Date:
2025-12-25 @ 12:44 AM
Ignite Modification Date:
2026-01-26 @ 3:25 AM
Study NCT ID:
NCT04172467
Status:
COMPLETED
Last Update Posted:
2022-01-10
First Post:
2019-11-19
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Quality Assurance of Secondary Immunodeficiencies (SID) in CLL/MM Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015451', 'term': 'Leukemia, Lymphocytic, Chronic, B-Cell'}, {'id': 'D009101', 'term': 'Multiple Myeloma'}], 'ancestors': [{'id': 'D015448', 'term': 'Leukemia, B-Cell'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D054219', 'term': 'Neoplasms, Plasma Cell'}, {'id': 'D020141', 'term': 'Hemostatic Disorders'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D010265', 'term': 'Paraproteinemias'}, {'id': 'D001796', 'term': 'Blood Protein Disorders'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'praxis-link@kabelmail.de', 'phone': '0631', 'title': 'Prof. Hartmut Link', 'phoneExt': '3503709', 'organization': 'Hematology Oncology Kaiserslautern'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'The limitations of the retrospective study are that the information in the patient records cannot be verified and that the diagnosis and monitoring of the patients are not specified. In the case of infections, the classification was missing for a large number of patients.'}}, 'adverseEventsModule': {'timeFrame': '12 months', 'description': 'Since this is an observational study of clinical routine, there is no studied medicinal product involved in this study and no safety event were extracted as part of this study.', 'eventGroups': [{'id': 'EG000', 'title': 'Non-interventional Retropspective Observational Study.', 'description': 'Data from 1086 patients (CLL 490, MM 596) were collected from 86 centres.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Guideline Adherence (GLAD)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1086', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Non-interventional Retrospective Observational Study.', 'description': 'This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analysed.'}], 'classes': [{'categories': [{'title': 'GLAD-Score 2', 'measurements': [{'value': '889', 'groupId': 'OG000'}]}, {'title': 'GLAD-Score 1', 'measurements': [{'value': '75', 'groupId': 'OG000'}]}, {'title': 'GLAD-Score 0', 'measurements': [{'value': '122', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Median study observation period of 18.2 months', 'description': 'For SID, immunoglobulin substitution (IgRT) is mandatory only for patients with an IgG level \\< 4g/l (or IgG subclass deficiency) and additionally more than 3 infections or a severe infection (≥ grade 3) and is optional (may be appropriate) if IgG level \\< 4g/l and/or 1-3 less severe infections (≤ grade 2). IgRT is not indicated if patients do not fulfil either condition.\n\nScoring system:\n\nGLAD-Score 2: full guideline adherence GLAD-Score 1: deviations in dose or interval (+/- 10%) or a late start of IgRT (\\>28 days after a severe infection (≥ grade 3).\n\nGLAD-Score 0: IgRT without indication (overuse) or omitted IgRT despite recommendation (underuse). Likewise, 0 points were awarded if both the dose and the interval deviated from the GL recommendations (e.g. underdosed single dose) or if IgRT was not started until more than 3 months after hypogammaglobulinemia and at least one severe infection.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Guideline Adherence and Susceptibility to Infection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '889', 'groupId': 'OG000'}, {'value': '75', 'groupId': 'OG001'}, {'value': '122', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'GLAD-Score 2', 'description': '2 points for full GLAD'}, {'id': 'OG001', 'title': 'GLAD-Score 1', 'description': '1 point for deviations in dose or interval (+/- 10%) or a late start of IgRT (\\>28 days after a severe infection (≥ grade 3)'}, {'id': 'OG002', 'title': 'GLAD-Score 0', 'description': '0 points for IgRT without indication (overuse) or omitted IgRT despite recommendation (underuse). Likewise, 0 points were awarded if both the dose and the interval deviated from the GL recommendations (e.g. underdosed single dose) or if IgRT was not started until more than 3 months after hypogammaglobulinemia and at least one severe infection'}], 'classes': [{'categories': [{'measurements': [{'value': '250', 'groupId': 'OG000'}, {'value': '63', 'groupId': 'OG001'}, {'value': '221', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '4.49', 'ciLowerLimit': '3.72', 'ciUpperLimit': '5.42', 'pValueComment': 'For effect estimation, hazard ratios are reported with 95% confidence interval. The significance level is set to two-sided ≤ 5% (p ≤ 0.05).', 'groupDescription': 'For the analysis of susceptibility to infection, the time to next infection was examined using the Andersen-Gill model. This model is an extension to the proportional hazard model (Cox model) for time to recurrent event analysis. The null hypothesis is that the GLAD-Score has no effect on susceptibility to infection.', 'statisticalMethod': 'Regression, Cox', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'The Model developed by Anderson and Gill (1982) is an extension to the proportional hazard model (Cox model) for time to recurrent event analysis.', 'nonInferiorityComment': 'To estimate the relevance of guideline adherent treatment (GLAD) for the susceptibility to infection, full GLAD is taken as reference category.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '2.52', 'ciLowerLimit': '1.98', 'ciUpperLimit': '3.21', 'pValueComment': 'For effect estimation, hazard ratios are reported with 95% confidence interval. The significance level is set to two-sided ≤ 5% (p ≤ 0.05).', 'groupDescription': 'For the analysis of susceptibility to infection, the time to next infection was examined using the Andersen-Gill model. This model is an extension to the proportional hazard model (Cox model) for time to recurrent event analysis. The null hypothesis is that the GLAD-Score has no effect on susceptibility to infection.', 'statisticalMethod': 'Regression, Cox', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'The Model developed by Anderson and Gill (1982) is an extension to the proportional hazard model (Cox model) for time to recurrent event analysis.', 'nonInferiorityComment': 'To estimate the relevance of guideline adherent treatment (GLAD) for the susceptibility to infection, full GLAD is taken as reference category.'}], 'paramType': 'NUMBER', 'timeFrame': 'Median study observation period of 18.2 months', 'description': 'For the analysis of susceptibility to infection, the time to next infection was examined using the Andersen-Gill model for recurrent events. For effect estimation, hazard ratios are reported with 95% confidence interval in each case. GLAD-Score 2 is Reference, a higher hazard ratio means a higher susceptibility to infection.', 'unitOfMeasure': 'Number of infectious events', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Not Applicable. Non-interventional Retropspective Observational Study.', 'description': 'This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analysed.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1086'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1086'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'This is a retrospective sample analysis of patients from practices and hospitals in Germany who were representatively screened using previously collected care parameters of the participating institutions. Previous and current treatment and infection data were collected from patients who received a line of therapy for the treatment of CLL or MM started in 2018 (1st, 2nd and 3rd or higher line).', 'preAssignmentDetails': 'The time period was chosen to ensure that patients have been followed up for at least 12 months in order to collect data on susceptibility to infection and possible secondary immunodeficiencies'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '1086', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Non-interventional Retrospective Observational Study.', 'description': 'This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analysed.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '267', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '819', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '73', 'groupId': 'BG000', 'lowerLimit': '33', 'upperLimit': '93'}]}]}], 'paramType': 'MEAN', 'description': 'Age at the start of the therapy line under investigation', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '475', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '611', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1086', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Germany', 'categories': [{'measurements': [{'value': '1086', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'This was a retrospective sample analysis of patients from practices and hospitals in Germany who were representatively screened using previously collected care parameters of the participating institutions. Previous and current treatment and infection data were collected from patients who received a line of therapy for the treatment of CLL or MM started in 2018 (1st, 2nd and 3rd or higher line). The time period was chosen to ensure that patients have been followed up for at least 12 months in order to collect data on susceptibility to infection and possible secondary immunodeficiencies.', 'unitOfMeasure': 'Participants'}, {'title': 'Therapy Line', 'classes': [{'categories': [{'title': '1st line', 'measurements': [{'value': '539', 'groupId': 'BG000'}]}, {'title': '2nd line', 'measurements': [{'value': '317', 'groupId': 'BG000'}]}, {'title': '3rd line', 'measurements': [{'value': '230', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Disease', 'classes': [{'categories': [{'title': 'Chronic Lymphocytic Leukaemia (CLL)', 'measurements': [{'value': '490', 'groupId': 'BG000'}]}, {'title': 'Multiple Myeloma (MM)', 'measurements': [{'value': '596', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Patients with chronic lymphocytic leukaemia and multiple myeloma and systemic treatment in 2018'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-05-16', 'size': 343339, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2021-11-09T11:57', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'OTHER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1086}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-01-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-11', 'completionDateStruct': {'date': '2020-08-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-11-10', 'studyFirstSubmitDate': '2019-11-19', 'resultsFirstSubmitDate': '2021-09-10', 'studyFirstSubmitQcDate': '2019-11-19', 'lastUpdatePostDateStruct': {'date': '2022-01-10', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-11-10', 'studyFirstPostDateStruct': {'date': '2019-11-21', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2022-01-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-04-25', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Guideline Adherence (GLAD)', 'timeFrame': 'Median study observation period of 18.2 months', 'description': 'For SID, immunoglobulin substitution (IgRT) is mandatory only for patients with an IgG level \\< 4g/l (or IgG subclass deficiency) and additionally more than 3 infections or a severe infection (≥ grade 3) and is optional (may be appropriate) if IgG level \\< 4g/l and/or 1-3 less severe infections (≤ grade 2). IgRT is not indicated if patients do not fulfil either condition.\n\nScoring system:\n\nGLAD-Score 2: full guideline adherence GLAD-Score 1: deviations in dose or interval (+/- 10%) or a late start of IgRT (\\>28 days after a severe infection (≥ grade 3).\n\nGLAD-Score 0: IgRT without indication (overuse) or omitted IgRT despite recommendation (underuse). Likewise, 0 points were awarded if both the dose and the interval deviated from the GL recommendations (e.g. underdosed single dose) or if IgRT was not started until more than 3 months after hypogammaglobulinemia and at least one severe infection.'}], 'secondaryOutcomes': [{'measure': 'Guideline Adherence and Susceptibility to Infection', 'timeFrame': 'Median study observation period of 18.2 months', 'description': 'For the analysis of susceptibility to infection, the time to next infection was examined using the Andersen-Gill model for recurrent events. For effect estimation, hazard ratios are reported with 95% confidence interval in each case. GLAD-Score 2 is Reference, a higher hazard ratio means a higher susceptibility to infection.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Secondary immunodeficiencies (SID)', 'Chronic lymphocytic leukemia (CLL)', 'Multiple myeloma (MM)'], 'conditions': ['Secondary Immunodeficiencies (SID)']}, 'descriptionModule': {'briefSummary': 'Retrospective, representative registry for quality assurance on diagnosis and therapy of secondary immunodeficiencies (SID) in patients with chronic lymphocytic leukemia (CLL) or multiple myeloma (MM)', 'detailedDescription': "Treatment structure analysis and recruitment (phase 1):\n\nIn a first step, data on care facilities, that treat patients with CLL or MM in Germany is obtained.\n\nIn phase 1 all centers in Germany that potentially treat patients with the CLL or MM are contacted and data of its facility care level and its number of treated patients is recorded using a one-sided pen-to-paper form. In addition, the willingness of care facilities to become involved in patients' documentation is elicited (phase 2).\n\nPatient documentation (phase 2)\n\nTo achieve a reliable, representative sample of patients treated in Germany, the distribution of cases to be documented is specified in the individual indications amongst the facilities involved. This is done using the facilities' data on patient numbers and treatment structure obtained in phase I:\n\nThe participating centers are assigned to clusters based on key distinguishing features (facility type, care level and number of patients treated). This sample is modulated according to the previous treatment structure analysis. By taking this approach, the actual percentages of the various care facilities in an indication area can be reflected proportionally in the patient documentation sample.\n\nIn phase 2 a electronic case record form (eCRF) is completed in order to collect the original patient and treatment data, which are relevant to the purpose of the study. All data is gathered retrospectively and anonymously using the patient files. Patient and disease related variables (age, general condition according to the Eastern Cooperative Oncology Group (ECOG), relevant comorbidity, staging and relevant mutations), systemic antineoplastic treatment (chemotherapy, antibodies, kinase-inhibitors, relevant co-medication etc.) are recorded. Also, data on diagnosis of Ig-levels (IgG, IgA, IgM), therapy of secondary immunodeficiencies as well as the number and severity of occurred infections and their treatment is collected. Clusters for classification of infections will be developed (e.g. life-threatening, need for hospitalization).\n\nIn order to ensure data quality, the scientific project lead will provide training for two employees of the commissioned institute on matters regarding the content of the study. This knowledge will be incorporated into the programming of the user interface and the patient databases so that the program will check for completeness and, as far as possible, plausibility, on the basis of defined requirements and constraints. These checks accompany the process of entering data into the eCRF and allow for validating data instantly. If inconsistencies, mistakes or omissions are detected, data will be validated by an integrated query management system.\n\nPhysicians questionnaire (phase 3)\n\nIn an additional step and alongside the patient documentation, the attending physicians in participating centers will be surveyed (phase 3) on their competency profile, their assessment of guideline quality and their approach to avoid infections of CLL and MM patients."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with chronic lymphocytic leukemia (CLL) or multiple myeloma (MM).', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients with CLL or MM\n* anti-neoplastic systemic therapy (all therapy lines) between July 1st 2017 and June 30th 2018\n\nExclusion Criteria:\n\n\\- patient in terminal phase of the disease, life expectancy less than three months'}, 'identificationModule': {'nctId': 'NCT04172467', 'acronym': 'QS-SID', 'briefTitle': 'Quality Assurance of Secondary Immunodeficiencies (SID) in CLL/MM Patients', 'organization': {'class': 'OTHER', 'fullName': 'AIO-Studien-gGmbH'}, 'officialTitle': 'Quality Assurance on Diagnosis and Therapy of Secondary Immunodeficiencies (SID) in Patients With Chronic Lymphocytic Leukemia (CLL) or Multiple Myeloma (MM) in Germany (QS-SID)', 'orgStudyIdInfo': {'id': 'AIO-SUP-0119ass (QS SID)'}}, 'armsInterventionsModule': {'interventions': [{'name': 'non-interventional retrospective epidemiological observational study', 'type': 'OTHER', 'description': 'non-interventional retrospective epidemiological observational study'}]}, 'contactsLocationsModule': {'locations': [{'zip': '67655', 'city': 'Kaiserslautern', 'country': 'Germany', 'facility': 'Privatärztliche Praxis; Innere Medizin, Hämatologie, Internistische Onkologie', 'geoPoint': {'lat': 49.443, 'lon': 7.77161}}], 'overallOfficials': [{'name': 'Hartmut Link, Prof. Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'AIO AG Supportive Therapie'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Data is collected retrospectively and completely anonymously from patient records, no identifying characteris-tics (e.g. birth date, initial letters, pseudonym) will be collected.\n\nIt is hoped that these data will assist in creating new possibilities and ways to improve the quality of treatment through further training and enhancement of the availability and transparency of the guidelines.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'AIO-Studien-gGmbH', 'class': 'OTHER'}, 'collaborators': [{'name': 'Prof. Hartmut Link', 'class': 'UNKNOWN'}, {'name': 'Takeda', 'class': 'INDUSTRY'}, {'name': 'MMF GmbH', 'class': 'INDUSTRY'}, {'name': 'AIO AG Supportivtherapie', 'class': 'OTHER'}, {'name': 'AG Supportive Maßnahmen in der Onkologie', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}