Screening for AL Amyloidosis in Smoldering Multiple Myeloma

NCT ID: NCT06365060

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2029-02-27

Brief Summary

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.

Detailed Description

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.

Conditions

Smoldering Multiple Myeloma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients 40 years of age and older
• diagnosed with either Smoldering Multiple Myeloma or a Monoclonal Gammopathy
• dFLC greater than 23 mg/L
• abnormal FLC ratio
• 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.

Exclusion Criteria

• Patients younger than 40 years of age are not eligible
• Patients with a previous finding of amyloid in other biopsies will not be included
• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama Hospital

Birmingham, Alabama, United States

Site Status: RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Cleveland Clinic Florida, Weston Hospital

Weston, Florida, United States

Site Status: RECRUITING

Tufts Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status: RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status: RECRUITING

UNC Lineberger Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status: RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status: RECRUITING

UT Southwestern, Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Site Status: NOT_YET_RECRUITING

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status: RECRUITING

VCU Medical Center

Richmond, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Raymond Comenzo, MD

Role: CONTACT

raymond.comenzo@tuftsmedicine.org

617-636-6454

Denis Toskic, BS

Role: CONTACT

denis.toskic@tuftsmedicine.org

617-636-5907

Facility Contacts

Megan Maier

Role: primary

mmaier@uabmc.edu

205-882-1041

Jane Greenaway

Role: primary

jane.greenaway@ucsf.edu

415-269-8259

Denis Toskic

Role: primary

denis.toskic@tuftsmedicine.org

617-636-5907

CUIMC Navigators

Role: primary

cancerclinicaltrials@cumc.columbia.edu

Bayley Axelrod

Role: primary

axelrodb@mskcc.org

Courtney Schepel

Role: primary

courtney.schepel@atriumhealth.org

980-292-0817

Kendall Conder

Role: primary

Kendall_Conder@med.unc.edu

919-962-7473

Sharmilee Nuli

Role: primary

sharmilee.nuli@hci.utah.edu

801-213-6203

Tyler Phillips

Role: primary

phillipst5@vcu.edu

804-828-9085

References

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.

Reference Type: BACKGROUND

PMID: 25916593 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19291508 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27891446 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10468868 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11468171 (View on PubMed)

Chaulagain CP, Comenzo RL. How we treat systemic light-chain amyloidosis. Clin Adv Hematol Oncol. 2015 May;13(5):315-24.

Reference Type: BACKGROUND

PMID: 26352777 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25734799 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17942755 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9578896 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25111004 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20425398 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17582068 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23183428 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12130507 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22067386 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15855274 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31189919 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18216299 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22100494 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24723680 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18945993 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27473738 (View on PubMed)

Other Identifiers

R01CA279808

Identifier Type: NIH

Identifier Source: secondary_id

View Link

00003143

Identifier Type: -

Identifier Source: org_study_id