Ignite Creation Date:
2025-12-24 @ 5:36 PM
Ignite Modification Date:
2025-12-29 @ 12:00 PM
Study NCT ID:
NCT04237168
Status:
UNKNOWN
Last Update Posted:
2020-01-29
First Post:
2020-01-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016403', 'term': 'Lymphoma, Large B-Cell, Diffuse'}], 'ancestors': [{'id': 'D016393', 'term': 'Lymphoma, B-Cell'}, {'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2020-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-01', 'completionDateStruct': {'date': '2022-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-01-27', 'studyFirstSubmitDate': '2020-01-17', 'studyFirstSubmitQcDate': '2020-01-17', 'lastUpdatePostDateStruct': {'date': '2020-01-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-01-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Clinical impact of the described technique for minimal residual disease (MRD) detection in patients with DLBCL', 'timeFrame': '3 years', 'description': 'The clonotype-derived sequences identified at diagnosis would be used as a target to assess the presence of MRD in follow-up samples and correlate it with clinical outcome.'}, {'measure': 'Feasibility of the described technique', 'timeFrame': '3 years', 'description': 'Sensitivity, specificity, and positive and negative predictive value of ctDNA detection will be assessed on the basis of the final determinations of ctDNA, at time points described.'}], 'primaryOutcomes': [{'measure': 'Association between ctDNA level and clinical response at the end of treatment', 'timeFrame': '12-18 months', 'description': 'Correlation between ctDNA level (in nanograms) and clinical response per PET/CT at the end of treatment (responses will be defined according to International Working Group consensus response evaluation criteria in lymphoma - IWGRECIL - 2017) will be assessed by means of Spearman correlation.'}], 'secondaryOutcomes': [{'measure': 'Correlation between detection of tumor clonotype ctDNA and relapse', 'timeFrame': '18 months', 'description': 'The relationship between detection of tumor clonotype ctDNA (detection: yes/no, using a frequency threshold of 5%) and relapse (disease status will be assessed by PET/CT) will be measured by means of a logistic regression model. These analyses are explorative and will be done if possible.'}, {'measure': 'Impact of IgNGS at the end of treatment and 6 months after treatment on outcome (as measured by progression-free survival PFS)', 'timeFrame': '18 months', 'description': 'The relationship between impact of IgNGS (ctDNA level in nanograms, detection of tumor clonotype: yes/no, relative frequency of index sequences in %) with PFS will be assessed by means of a Proportional-hazards (PH) Cox regression model. These analyses are explorative and will be done if possible.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Diffuse large B cell lymphoma', 'immunoglobulin gene next generation sequencing', 'liquid biopsy'], 'conditions': ['Lymphoma, Large B-Cell, Diffuse']}, 'referencesModule': {'references': [{'pmid': '28933999', 'type': 'BACKGROUND', 'citation': 'Herrera AF, Armand P. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications. J Clin Oncol. 2017 Dec 1;35(34):3877-3887. doi: 10.1200/JCO.2017.74.5281. Epub 2017 Sep 21.'}, {'pmid': '27831904', 'type': 'BACKGROUND', 'citation': 'Scherer F, Kurtz DM, Newman AM, Stehr H, Craig AF, Esfahani MS, Lovejoy AF, Chabon JJ, Klass DM, Liu CL, Zhou L, Glover C, Visser BC, Poultsides GA, Advani RH, Maeda LS, Gupta NK, Levy R, Ohgami RS, Kunder CA, Diehn M, Alizadeh AA. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med. 2016 Nov 9;8(364):364ra155. doi: 10.1126/scitranslmed.aai8545.'}, {'pmid': '28600337', 'type': 'BACKGROUND', 'citation': 'Scherer F, Kurtz DM, Diehn M, Alizadeh AA. High-throughput sequencing for noninvasive disease detection in hematologic malignancies. Blood. 2017 Jul 27;130(4):440-452. doi: 10.1182/blood-2017-03-735639. Epub 2017 Jun 9.'}, {'pmid': '25887775', 'type': 'BACKGROUND', 'citation': 'Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, Takahashi K, Glover C, Keane C, Kihira S, Visser B, Callahan J, Kong KA, Faham M, Corbelli KS, Miklos D, Advani RH, Levy R, Hicks RJ, Hertzberg M, Ohgami RS, Gandhi MK, Diehn M, Alizadeh AA. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood. 2015 Jun 11;125(24):3679-87. doi: 10.1182/blood-2015-03-635169. Epub 2015 Apr 17.'}, {'pmid': '25842160', 'type': 'BACKGROUND', 'citation': 'Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015 May;16(5):541-9. doi: 10.1016/S1470-2045(15)70106-3. Epub 2015 Apr 1.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.', 'detailedDescription': 'In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.\n\nDiffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (\\>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'newly DLBCL patients (diagnosed and treated in "Hospital de la Santa Creu i Sant Pau")', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria: patients diagnosed with de novo DLBCL, all ages, treated with R-CHOP. Patients with DLBCL not otherwise specified (NOS) according to World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO) 2016 would be included. In addition, those with "high-grade B cell lymphoma (including both NOS and those with Myc and bcl2 and/or bcl6 alterations) will be also included.\n\nExclusion Criteria:\n\n* Primary mediastinal DLBCL.\n* Transformed DLBCL\n* Patients HIV+\n* Central Nervous System (CNS) DLBCL\n* All other DLBCL not included under "NOS" classification, according to WHO 2016 (except those specifically indicated in "inclusion criteria").'}, 'identificationModule': {'nctId': 'NCT04237168', 'briefTitle': 'Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)', 'organization': {'class': 'OTHER', 'fullName': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau"}, 'officialTitle': 'Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL): Prognostic Implications and Assessment of Tumor Response', 'orgStudyIdInfo': {'id': 'IIBSP-LIN-2019-83'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'DLBCL patients', 'description': 'newly diagnosed DLBCL (de novo, all ages) patients treated with RCHOP (first-line treatment regimen)', 'interventionNames': ['Diagnostic Test: IgNGS from circulating tumor DNA']}], 'interventions': [{'name': 'IgNGS from circulating tumor DNA', 'type': 'DIAGNOSTIC_TEST', 'description': '3 longitudinal plasma samples will be evaluated at three different time points per patient: 0 (pre-treatment), end of treatment, and at 6 months after treatment.', 'armGroupLabels': ['DLBCL patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '08041', 'city': 'Barcelona', 'country': 'Spain', 'contacts': [{'name': 'Javier Briones, PhD', 'role': 'CONTACT', 'email': 'jbriones@santpau.cat'}, {'name': 'Anna Monter-Rovira, MD', 'role': 'CONTACT', 'email': 'amonter@santpau.cat'}, {'name': 'Javier Briones, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Anna Monter-Rovira, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marta Pratcorona, PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Anna Mozos, PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Josep F Nomdedéu, PhD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Hospital de la Santa Creu i Sant Pau', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}], 'centralContacts': [{'name': 'Javier Briones, PhD', 'role': 'CONTACT', 'email': 'jbriones@santpau.cat', 'phone': '+34935565649'}, {'name': 'Anna Monter-Rovira, MD', 'role': 'CONTACT', 'email': 'amonter@santpau.cat'}], 'overallOfficials': [{'name': 'Javier Briones', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'relevant results will be published in scientific journals available to all researchers.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau", 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}