Ignite Creation Date:
2025-12-25 @ 5:09 AM
Ignite Modification Date:
2025-12-26 @ 4:13 AM
Study NCT ID:
NCT04807127
Status:
RECRUITING
Last Update Posted:
2024-07-01
First Post:
2021-03-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D017563', 'term': 'Lung Diseases, Interstitial'}], 'ancestors': [{'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000082082', 'term': 'Immune Checkpoint Inhibitors'}, {'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'C000613593', 'term': 'durvalumab'}, {'id': 'D011878', 'term': 'Radiotherapy'}], 'ancestors': [{'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}, {'id': 'D000074322', 'term': 'Antineoplastic Agents, Immunological'}, {'id': 'D000970', 'term': 'Antineoplastic Agents'}, {'id': 'D045506', 'term': 'Therapeutic Uses'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': '* BAL samples will not be retained\n* PBMC samples will be stored at -80°C, for batch processing'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-02-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-06', 'completionDateStruct': {'date': '2025-01-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-06-28', 'studyFirstSubmitDate': '2021-03-10', 'studyFirstSubmitQcDate': '2021-03-18', 'lastUpdatePostDateStruct': {'date': '2024-07-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-03-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-01-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis BAL fluid', 'timeFrame': 'From date of inclusion until study completion, on average 2 years', 'description': 'By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets'}, {'measure': 'Differentially expressed genes in BAL fluid, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis', 'timeFrame': 'From date of inclusion until study completion, on average 2 years', 'description': 'By identifying differentially expressed genes in ICI- vs. RT- vs. TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets'}], 'secondaryOutcomes': [{'measure': 'Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells', 'timeFrame': 'From date of inclusion until study completion, on average 2 years', 'description': 'By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets'}, {'measure': 'Differentially expressed genes in PBMC, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis', 'timeFrame': 'From date of inclusion until study completion, on average 2 years', 'description': 'By identifying differentially expressed genes in ICI- vs. RT- vs. TKI-induced pneumonitis PBMC, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Pneumonitis, Interstitial', 'Immunotherapy', 'Immune-related Adverse Events']}, 'descriptionModule': {'briefSummary': 'The main goal of this prospective non-interventional exploratory monocentric study is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from cancer patients experiencing cancer therapy-induced pneumonitis on a single-cell scale. These mechanistic insights can directly lead to putative diagnostic biomarkers and therapeutic targets.\n\nA second highly clinically relevant hypothesis is that single-cell profiling of blood samples will reveal circulating biomarkers of ICB toxicity, making non-invasive diagnosis feasible.', 'detailedDescription': 'The investigators will apply single cell RNA- and TCR-sequencing on up to 5,000 single cells per sample. Additionally, cell surface protein expression can be integrated with the transcriptional information. Various bioinformatics pipelines, including Seurat, will be used to identify different cell clusters, which through marker gene expression will be assigned to known cell types, cellular subtypes or phenotypes. For instance, this will make it possible to monitor the abundance of PD-1/PD-L1 expressing T-cells, cytotoxic T-cells, immune-suppressive myeloid cells etc. The following parameters at single-cell level will be relevant, amongst others:\n\n* The composition and relative abundancies of established immune cell types (e.g. T cells (CD4+, CD8+ and regulatory subsets), NK cells, B cells, MDSCs, macrophages, neutrophils, dendritic cells). Transcriptomic data for each of these immune cell subtypes will be analyzed, allowing characterization of specific gene expression programs that define specific phenotypic states.\n* Composition of all stromal cellular subtypes identified by single-cell transcriptomics.\n* A gene regulatory network for each cell type and cellular subtype (or cell state) will be established and master transcriptional regulators will be identified. Individual T-cells and T-cell subclusters will be classified based on interferon activation, high rates of proliferation and transcription and increased granzyme expression, which are all indicative of T-cell activation.\n\nBlood samples will be subjected to similar single-cell experimental procedures. First, peripheral blood mononuclear cells (PBMC) are isolated using Ficoll density gradient centrifugation. Single-cell transcriptome analysis in combination with CITE-seq will be performed on 5000 PBMC. Cellular composition will be determined using the same bioinformatic pipelines as used for processing the BAL fluid cells.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '120 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients experiencing cancer-treatment induced pneumonitis, undergoing bronchoscopy with BAL', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria:\n\n* Adult M/F/X (\\>= 18 years)\n* Patients receiving or having received treatment per guidelines\n* Patients undergoing bronchoscopy with BAL, for possible cancer treatment-induced pneumonitis\n* Not included in other clinical trials\n* Signed informed consent form\n\nExclusion criteria:\n\n• Collected material not suitable for further processing in this study (e.g. bad quality). This decision will be made in consultation with a lab technician and/or bio-informatician, specialized in single-cell analysis.'}, 'identificationModule': {'nctId': 'NCT04807127', 'briefTitle': 'A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade', 'organization': {'class': 'OTHER', 'fullName': 'Universitaire Ziekenhuizen KU Leuven'}, 'officialTitle': 'A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade', 'orgStudyIdInfo': {'id': 'S63357'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'ICI-pneumonitis', 'description': 'Cancer patients experiencing ICI-pneumonitis', 'interventionNames': ['Drug: Immune checkpoint blockade']}, {'label': 'Radiotherapy induced pneumonitis', 'description': 'Cancer patients experiencing RT-pneumonitis', 'interventionNames': ['Radiation: Radiotherapy']}, {'label': 'TKI-induced pneumonitis', 'description': 'Cancer patients experiencing TKI-induced pneumonitis', 'interventionNames': ['Drug: Targeted therapy']}], 'interventions': [{'name': 'Immune checkpoint blockade', 'type': 'DRUG', 'otherNames': ['Pembrolizumab', 'Durvalumab'], 'description': 'ICI, administered as standard-of-care treatment', 'armGroupLabels': ['ICI-pneumonitis']}, {'name': 'Targeted therapy', 'type': 'DRUG', 'otherNames': ['TKI'], 'description': 'TKI, administered as standard-of-care treatment', 'armGroupLabels': ['TKI-induced pneumonitis']}, {'name': 'Radiotherapy', 'type': 'RADIATION', 'description': 'RT, administered as standard-of-care treatment', 'armGroupLabels': ['Radiotherapy induced pneumonitis']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3000', 'city': 'Leuven', 'state': 'Flemish Brabant', 'status': 'RECRUITING', 'country': 'Belgium', 'contacts': [{'name': 'Els Wauters, MD, PhD', 'role': 'CONTACT', 'email': 'els.wauters@uzleuven.be', 'phone': '016340942'}], 'facility': 'Universitaire Ziekenhuizen Leuven', 'geoPoint': {'lat': 50.87959, 'lon': 4.70093}}], 'centralContacts': [{'name': 'Els Wauters, MD, PhD', 'role': 'CONTACT', 'email': 'els.wauters@uzleuven.be', 'phone': '+3216340942'}], 'overallOfficials': [{'name': 'Els Wauters, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospitals - KU Leuven'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universitaire Ziekenhuizen KU Leuven', 'class': 'OTHER'}, 'collaborators': [{'name': 'KU Leuven', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}