Ignite Creation Date:
2025-12-25 @ 2:10 AM
Ignite Modification Date:
2025-12-27 @ 6:29 AM
Study NCT ID:
NCT06365060
Status:
RECRUITING
Last Update Posted:
2025-08-06
First Post:
2024-04-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Screening for AL Amyloidosis in Smoldering Multiple Myeloma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000075122', 'term': 'Smoldering Multiple Myeloma'}, {'id': 'D000075363', 'term': 'Immunoglobulin Light-chain Amyloidosis'}], 'ancestors': [{'id': 'D011230', 'term': 'Precancerous Conditions'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006942', 'term': 'Hypergammaglobulinemia'}, {'id': 'D001796', 'term': 'Blood Protein Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D010265', 'term': 'Paraproteinemias'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D054219', 'term': 'Neoplasms, Plasma Cell'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D000686', 'term': 'Amyloidosis'}, {'id': 'D057165', 'term': 'Proteostasis Deficiencies'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'cDNA derived from bone marrow CD138-selected plasma cells.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 400}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-05-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2029-02-27', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-01', 'studyFirstSubmitDate': '2024-04-10', 'studyFirstSubmitQcDate': '2024-04-10', 'lastUpdatePostDateStruct': {'date': '2025-08-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-04-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-02-27', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Creating a network to enroll patients on a collaborative study requiring marrow and blood specimens, to collect data for a training set of likelihood statistics and to plan a future validation study.', 'timeFrame': '5 years', 'description': 'With a 15-center network covering 12 states and almost 45% of the US population, we will evaluate 400 SMM patients \\> 40 years old who pass FLC criteria using standard of care tests including NT-proBNP and clinical marrow specimens evaluated for the presence of t(11;14) and gain1q. Marrow cells will be processed by NGS for clonal IGLV gene identification. With the training data obtained, we will use existing statistical modeling techniques to generate a statistical algorithm for identifying undiagnosed cases of AL and assessment of risk of AL, and to plan a validation study testing the training model. We will also investigate a role for the novel biomarker clusterin (Clu) as an indicator of risk of AL in SMM patients; preliminary work indicates that Clu is significantly lower in AL than in SMM patients.'}, {'measure': 'Validating an NGS assay that identifies IGLV genes in clonal plasma cells', 'timeFrame': '5 years', 'description': 'All subjects will have their clonal IGLV genes identified by NGS enabling the creation and validation of a laboratory developed test in a precision medicine laboratory that is certified under regulations of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Approval for this laboratory developed test for both κ and λ IGVL genes will permit providers, patients and researchers to use the test in decision-making to care for monoclonal gammopathy patients. We will also investigate the exploratory objective of defining the alterations in sequence in AL and non-AL FLC derived from the same IGLV germline gene.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['SMM', 'AL Amyloidosis'], 'conditions': ['Smoldering Multiple Myeloma']}, 'referencesModule': {'references': [{'pmid': '25916593', 'type': 'BACKGROUND', 'citation': 'Avalos M, Pouyes H, Grandvalet Y, Orriols L, Lagarde E. Sparse conditional logistic regression for analyzing large-scale matched data from epidemiological studies: a simple algorithm. BMC Bioinformatics. 2015;16 Suppl 6(Suppl 6):S1. doi: 10.1186/1471-2105-16-S6-S1. Epub 2015 Apr 17.'}, {'pmid': '19291508', 'type': 'BACKGROUND', 'citation': 'Bodi K, Prokaeva T, Spencer B, Eberhard M, Connors LH, Seldin DC. AL-Base: a visual platform analysis tool for the study of amyloidogenic immunoglobulin light chain sequences. Amyloid. 2009 Mar;16(1):1-8. doi: 10.1080/13506120802676781.'}, {'pmid': '27891446', 'type': 'BACKGROUND', 'citation': 'Bujang MA, Adnan TH. Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis. J Clin Diagn Res. 2016 Oct;10(10):YE01-YE06. doi: 10.7860/JCDR/2016/18129.8744. Epub 2016 Oct 1.'}, {'pmid': '10468868', 'type': 'BACKGROUND', 'citation': 'Comenzo RL, Wally J, Kica G, Murray J, Ericsson T, Skinner M, Zhang Y. Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br J Haematol. 1999 Sep;106(3):744-51. doi: 10.1046/j.1365-2141.1999.01591.x.'}, {'pmid': '11468171', 'type': 'BACKGROUND', 'citation': 'Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood. 2001 Aug 1;98(3):714-20. doi: 10.1182/blood.v98.3.714.'}, {'pmid': '26352777', 'type': 'BACKGROUND', 'citation': 'Chaulagain CP, Comenzo RL. How we treat systemic light-chain amyloidosis. Clin Adv Hematol Oncol. 2015 May;13(5):315-24.'}, {'pmid': '25734799', 'type': 'BACKGROUND', 'citation': 'Dasari S, Theis JD, Vrana JA, Meureta OM, Quint PS, Muppa P, Zenka RM, Tschumper RC, Jelinek DF, Davila JI, Sarangi V, Kurtin PJ, Dogan A. Proteomic detection of immunoglobulin light chain variable region peptides from amyloidosis patient biopsies. J Proteome Res. 2015 Apr 3;14(4):1957-67. doi: 10.1021/acs.jproteome.5b00015. Epub 2015 Mar 20.'}, {'pmid': '17942755', 'type': 'BACKGROUND', 'citation': 'Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, Clark RJ, Melton LJ 3rd, Gertz MA, Kumar SK, Fonseca R, Jelinek DF, Rajkumar SV. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008 Jan 15;111(2):785-9. doi: 10.1182/blood-2007-08-108357. Epub 2007 Oct 17.'}, {'pmid': '9578896', 'type': 'BACKGROUND', 'citation': 'Dubrey SW, Cha K, Anderson J, Chamarthi B, Reisinger J, Skinner M, Falk RH. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM. 1998 Feb;91(2):141-57. doi: 10.1093/qjmed/91.2.141.'}, {'pmid': '25111004', 'type': 'BACKGROUND', 'citation': 'Kourelis TV, Kumar SK, Go RS, Kapoor P, Kyle RA, Buadi FK, Gertz MA, Lacy MQ, Hayman SR, Leung N, Dingli D, Lust JA, Lin Y, Zeldenrust SR, Rajkumar SV, Dispenzieri A. Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias. Am J Hematol. 2014 Nov;89(11):1051-4. doi: 10.1002/ajh.23827. Epub 2014 Sep 2.'}, {'pmid': '20425398', 'type': 'BACKGROUND', 'citation': 'Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Curr Hematol Malig Rep. 2010 Apr;5(2):62-9. doi: 10.1007/s11899-010-0047-9.'}, {'pmid': '17582068', 'type': 'BACKGROUND', 'citation': 'Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, Larson DR, Plevak MF, Jelinek DF, Fonseca R, Melton LJ 3rd, Rajkumar SV. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007 Jun 21;356(25):2582-90. doi: 10.1056/NEJMoa070389.'}, {'pmid': '23183428', 'type': 'BACKGROUND', 'citation': 'Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013 Apr;27(4):941-6. doi: 10.1038/leu.2012.296. Epub 2012 Oct 16.'}, {'pmid': '12130507', 'type': 'BACKGROUND', 'citation': 'Perfetti V, Casarini S, Palladini G, Vignarelli MC, Klersy C, Diegoli M, Ascari E, Merlini G. Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood. 2002 Aug 1;100(3):948-53. doi: 10.1182/blood-2002-01-0114.'}, {'pmid': '22067386', 'type': 'BACKGROUND', 'citation': 'Perfetti V, Palladini G, Casarini S, Navazza V, Rognoni P, Obici L, Invernizzi R, Perlini S, Klersy C, Merlini G. The repertoire of lambda light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44. Blood. 2012 Jan 5;119(1):144-50. doi: 10.1182/blood-2011-05-355784. Epub 2011 Nov 8.'}, {'pmid': '15855274', 'type': 'BACKGROUND', 'citation': 'Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, Larson DR, Plevak MF, Dispenzieri A, Katzmann JA. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005 Aug 1;106(3):812-7. doi: 10.1182/blood-2005-03-1038. Epub 2005 Apr 26.'}, {'pmid': '31189919', 'type': 'BACKGROUND', 'citation': 'Tahir UA, Doros G, Kim JS, Connors LH, Seldin DC, Sam F. Predictors of Mortality in Light Chain Cardiac Amyloidosis with Heart Failure. Sci Rep. 2019 Jun 12;9(1):8552. doi: 10.1038/s41598-019-44912-x.'}, {'pmid': '18216299', 'type': 'BACKGROUND', 'citation': 'Zhou P, Comenzo RL, Olshen AB, Bonvini E, Koenig S, Maslak PG, Fleisher M, Hoffman J, Jhanwar S, Young JW, Nimer SD, Boruchov AM. CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy. Blood. 2008 Apr 1;111(7):3403-6. doi: 10.1182/blood-2007-11-125526. Epub 2008 Jan 23.'}, {'pmid': '22100494', 'type': 'BACKGROUND', 'citation': 'Zhou P, Hoffman J, Landau H, Hassoun H, Iyer L, Comenzo RL. Clonal plasma cell pathophysiology and clinical features of disease are linked to clonal plasma cell expression of cyclin D1 in systemic light-chain amyloidosis. Clin Lymphoma Myeloma Leuk. 2012 Feb;12(1):49-58. doi: 10.1016/j.clml.2011.09.217. Epub 2011 Nov 18.'}, {'pmid': '24723680', 'type': 'BACKGROUND', 'citation': 'Zhou P, Ma X, Iyer L, Chaulagain C, Comenzo RL. One siRNA pool targeting the lambda constant region stops lambda light-chain production and causes terminal endoplasmic reticulum stress. Blood. 2014 May 29;123(22):3440-51. doi: 10.1182/blood-2013-10-535187. Epub 2014 Apr 10.'}, {'pmid': '18945993', 'type': 'BACKGROUND', 'citation': 'Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, Cockwell P. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008 Nov;3(6):1684-90. doi: 10.2215/CJN.02290508.'}, {'pmid': '27473738', 'type': 'BACKGROUND', 'citation': 'Singh G. Serum Free Light Chain Assay and kappa/lambda Ratio Performance in Patients Without Monoclonal Gammopathies: High False-Positive Rate. Am J Clin Pathol. 2016 Aug;146(2):207-14. doi: 10.1093/ajcp/aqw099.'}]}, 'descriptionModule': {'briefSummary': 'In this multicenter study, we will recruit 400 patients 40 years of age or older at 15 centers with a diagnosis of smoldering multiple myeloma (SMM), a group of patients for whom standard of care is observation not treatment. The main goal of this study is to screen for the diagnosis of light-chain amyloidosis (AL) before the onset of symptomatic disease and to develop a training set for a likelihood algorithm.', 'detailedDescription': 'This study is based on results from two prior studies in which 4 of 36 patients with SMM and none of 14 patients with MGUS were found to have AL. The hypothesis that we test with this protocol is that patients with (1) a pre-existing diagnosis of SMM, (2) free light chain (FLC) abnormalities, (3) IGLV genes associated with AL,(4) t(11;14) or gain 1q, and (5) NT-proBNP \\> 332pg/mL will have undiagnosed AL or risk of progression to AL. We will study the potential for SMM, the FLC screen, AL-related IGLV gene use, t(11;14) or gain 1q cytogenetic abnormalities, and NT-proBNP \\> 332pg/mL to be the variables in a likelihood algorithm for AL.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Smoldering Multiple Myeloma patients.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients 40 years of age and older\n* diagnosed with either Smoldering Multiple Myeloma or a Monoclonal Gammopathy\n* dFLC greater than 23 mg/L\n* abnormal FLC ratio\n* If the patient has an eGFR less than 50 mL/min/1.73m2, the FLC ratio is inconsequential. The patient only needs to meet the age and dFLC criterion.\n\nExclusion Criteria:\n\n* Patients younger than 40 years of age are not eligible\n* Patients with a previous finding of amyloid in other biopsies will not be included\n* Adults unable to consent are not eligible, including the cognitively impaired Pregnant women, pregnant minors, minors (i.e., individuals who are not yet adults), wards of the state, non-viable neonates, neonates of uncertain viability, and prisoners are not eligible'}, 'identificationModule': {'nctId': 'NCT06365060', 'briefTitle': 'Screening for AL Amyloidosis in Smoldering Multiple Myeloma', 'organization': {'class': 'OTHER', 'fullName': 'Tufts Medical Center'}, 'officialTitle': 'Screening for AL Amyloidosis in Smoldering Multiple Myeloma', 'orgStudyIdInfo': {'id': '00003143'}, 'secondaryIdInfos': [{'id': 'R01CA279808', 'link': 'https://reporter.nih.gov/quickSearch/R01CA279808', 'type': 'NIH'}]}, 'contactsLocationsModule': {'locations': [{'zip': '35233', 'city': 'Birmingham', 'state': 'Alabama', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Megan Maier', 'role': 'CONTACT', 'email': 'mmaier@uabmc.edu', 'phone': '205-882-1041'}, {'name': 'Susan Bal, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Alabama Hospital', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '90048', 'city': 'Los Angeles', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Robert Vescio, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Cedars-Sinai Medical Center', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Jane Greenaway', 'role': 'CONTACT', 'email': 'jane.greenaway@ucsf.edu', 'phone': '415-269-8259'}, {'name': 'Tom Martin, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '33331', 'city': 'Weston', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Chakra Chaulagain, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Cleveland Clinic Florida, Weston Hospital', 'geoPoint': {'lat': 26.10037, 'lon': -80.39977}}, {'zip': '02111', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Denis Toskic', 'role': 'CONTACT', 'email': 'denis.toskic@tuftsmedicine.org', 'phone': '617-636-5907'}, {'name': 'Raymond Comenzo, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Tufts Medical Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'CUIMC Navigators', 'role': 'CONTACT', 'email': 'cancerclinicaltrials@cumc.columbia.edu'}, {'name': 'Suzanne Lentzsch, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Columbia University Irving Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Bayley Axelrod', 'role': 'CONTACT', 'email': 'axelrodb@mskcc.org'}, {'name': 'Heather Landau, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Memorial Sloan Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '28204', 'city': 'Charlotte', 'state': 'North Carolina', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Courtney Schepel', 'role': 'CONTACT', 'email': 'courtney.schepel@atriumhealth.org', 'phone': '980-292-0817'}, {'name': 'Cindy Varga, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Atrium Health Levine Cancer Institute', 'geoPoint': {'lat': 35.22709, 'lon': -80.84313}}, {'zip': '27705', 'city': 'Durham', 'state': 'North Carolina', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Kendall Conder', 'role': 'CONTACT', 'email': 'Kendall_Conder@med.unc.edu', 'phone': '919-962-7473'}, {'name': 'Sascha Tuchman, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'UNC Lineberger Comprehensive Cancer Center', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Naresh Bumma, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'The Ohio State University Comprehensive Cancer Center', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'status': 'NOT_YET_RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Larry Anderson, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'UT Southwestern, Harold C. Simmons Comprehensive Cancer Center', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Sharmilee Nuli', 'role': 'CONTACT', 'email': 'sharmilee.nuli@hci.utah.edu', 'phone': '801-213-6203'}, {'name': 'Amandeep Godara, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Utah, Huntsman Cancer Hospital', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '23219', 'city': 'Richmond', 'state': 'Virginia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Tyler Phillips', 'role': 'CONTACT', 'email': 'phillipst5@vcu.edu', 'phone': '804-828-9085'}, {'name': 'Hashim Mann, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'VCU Medical Center', 'geoPoint': {'lat': 37.55376, 'lon': -77.46026}}], 'centralContacts': [{'name': 'Raymond Comenzo, MD', 'role': 'CONTACT', 'email': 'raymond.comenzo@tuftsmedicine.org', 'phone': '617-636-6454'}, {'name': 'Denis Toskic, BS', 'role': 'CONTACT', 'email': 'denis.toskic@tuftsmedicine.org', 'phone': '617-636-5907'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tufts Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}