Screening for AL Amyloidosis in Smoldering Multiple Myeloma

April 10, 2024 updated by: Tufts Medical Center
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.

Study Overview

Status

Not yet recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama Hospital
        • Principal Investigator:
          • Susan Bal, MD
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
        • Principal Investigator:
          • Robert Vescio, MD
      • Orange, California, United States, 92868
        • University of California, Irvine
        • Principal Investigator:
          • Lisa Lee, MD
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
        • Principal Investigator:
          • Tom Martin, MD
    • Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida, Weston Hospital
        • Principal Investigator:
          • Chakra Chaulagain, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Giada Bianchi, MD
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
        • Principal Investigator:
          • Raymond Comenzo, MD
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
        • Principal Investigator:
          • Suzanne Lentzsch, MD
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Heather Landau, MD
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Atrium Health Levine Cancer Institute
        • Principal Investigator:
          • Cindy Varga, MD
      • Durham, North Carolina, United States, 27705
        • UNC Lineberger Comprehensive Cancer Center
        • Principal Investigator:
          • Sascha Tuchman, MD
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern, Harold C. Simmons Comprehensive Cancer Center
        • Principal Investigator:
          • Gurbakhash Kaur, MD
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah, Huntsman Cancer Hospital
        • Principal Investigator:
          • Amandeep Godara, MD
    • Virginia
      • Richmond, Virginia, United States, 23219
        • VCU Medical Center
        • Principal Investigator:
          • Hashim Mann, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Smoldering Multiple Myeloma patients.

Description

Inclusion Criteria:

  • Patients 40 years of age and older
  • diagnosed with Smoldering Multiple Myeloma
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
5 years
Validating an NGS assay that identifies IGLV genes in clonal plasma cells
Time Frame: 5 years
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.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tufts Medical Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

February 27, 2029

Study Completion (Estimated)

February 27, 2029

Study Registration Dates

First Submitted

April 10, 2024

First Submitted That Met QC Criteria

April 10, 2024

First Posted (Actual)

April 15, 2024

Study Record Updates

Last Update Posted (Actual)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00003143
  • R01CA279808 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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