AzTrials
AzTrials

Smoldering Multiple MyelomaNCT06365060

Screening for AL Amyloidosis in Smoldering Multiple Myeloma

An observational study of Smoldering Multiple Myeloma, run by Tufts Medical Center at 13 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Smoldering Multiple Myeloma
How many people
400 participants
Where
13 sitesUnited States
Study dates
1 May 2024to 27 Feb 2029
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Smoldering Multiple Myeloma patients.

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Raymond Comenzo, MD contact

617-636-6454

raymond.comenzo@tuftsmedicine.org

Denis Toskic, BS contact

617-636-5907

denis.toskic@tuftsmedicine.org

13 sites in 1 country

United States13 sites, 13 recruiting

  • University of Alabama Hospital

    Birmingham, Alabama, 35233

    Megan Maier, 205-882-1041, mmaier@uabmc.edu

    Susan Bal, MD

    Recruiting

  • Tufts Medical Center

    Boston, Massachusetts, 02111

    Denis Toskic, 617-636-5907, denis.toskic@tuftsmedicine.org

    Raymond Comenzo, MD

    Recruiting

  • Atrium Health Levine Cancer Institute

    Charlotte, North Carolina, 28204

    Courtney Schepel, 980-292-0817, courtney.schepel@atriumhealth.org

    Cindy Varga, MD

    Recruiting

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Naresh Bumma, MD

    Recruiting

  • UT Southwestern, Harold C. Simmons Comprehensive Cancer Center

    Dallas, Texas, 75390

    Larry Anderson, MD

    Not yet recruiting

  • UNC Lineberger Comprehensive Cancer Center

    Durham, North Carolina, 27705

    Kendall Conder, 919-962-7473, Kendall_Conder@med.unc.edu

    Sascha Tuchman, MD

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Robert Vescio, MD

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    CUIMC Navigators, cancerclinicaltrials@cumc.columbia.edu

    Suzanne Lentzsch, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Khayla Leiva, leivak@mskcc.org

    Heather Landau, MD

    Recruiting

  • VCU Medical Center

    Richmond, Virginia, 23219

    Zackary Moore, 804-628-1009, moorez@vcu.edu

    Hashim Mann, MD

    Recruiting

  • University of Utah, Huntsman Cancer Hospital

    Salt Lake City, Utah, 84112

    Sharmilee Nuli, 801-213-6203, sharmilee.nuli@hci.utah.edu

    Amandeep Godara, MD

    Recruiting

  • University of California, San Francisco

    San Francisco, California, 94143

    Ruixin Sun, 415-687-6084, Ruixin.Sun@ucsf.edu

    Tom Martin, MD

    Recruiting

  • Cleveland Clinic Florida, Weston Hospital

    Weston, Florida, 33331

    Chakra Chaulagain, MD

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Keywords
SMM, AL Amyloidosis
Medical subject headings
Smoldering Multiple Myeloma, Immunoglobulin Light-chain Amyloidosis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    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.

    Measured: 5 years

  2. Validating an NGS assay that identifies IGLV genes in clonal plasma cells

    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.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2024
  2. Study start1 May 2024
  3. Primary completion27 Feb 2029 (estimated)
  4. Study completion27 Feb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06365060
Sponsor's protocol ID
00003143
Other IDs
R01CA279808
Status last verified
Oct 2026
First submitted
10 Apr 2024
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 25916593

  • 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.

    PubMed 19291508

  • 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.

    PubMed 27891446

  • 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.

    PubMed 10468868

  • 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.

    PubMed 11468171

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

    PubMed 26352777

  • 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.

    PubMed 25734799

  • 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.

    PubMed 17942755

  • 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.

    PubMed 9578896

  • 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.

    PubMed 25111004

  • 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.

    PubMed 20425398

  • 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.

    PubMed 17582068

  • 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.

    PubMed 23183428

  • 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.

    PubMed 12130507

  • 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.

    PubMed 22067386

Questions about this trial

What is this clinical trial studying?

An observational study of Smoldering Multiple Myeloma, run by Tufts Medical Center at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Raymond Comenzo, MD (617-636-6454, raymond.comenzo@tuftsmedicine.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06365060, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in