Screening for AL Amyloidosis in Smoldering Multiple Myeloma
- Conditions
- Smoldering Multiple Myeloma
- Registration Number
- NCT06365060
- Lead Sponsor
- Tufts Medical Center
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- 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.
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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. 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.
Validating an NGS assay that identifies IGLV genes in clonal plasma cells 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 ฮบ and ฮป 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (13)
University of Alabama Hospital
๐บ๐ธBirmingham, Alabama, United States
Cedars-Sinai Medical Center
๐บ๐ธLos Angeles, California, United States
University of California, Irvine
๐บ๐ธOrange, California, United States
University of California, San Francisco
๐บ๐ธSan Francisco, California, United States
Cleveland Clinic Florida, Weston Hospital
๐บ๐ธWeston, Florida, United States
Tufts Medical Center
๐บ๐ธBoston, Massachusetts, United States
Columbia University Irving Medical Center
๐บ๐ธNew York, New York, United States
Memorial Sloan Kettering Cancer Center
๐บ๐ธNew York, New York, United States
Atrium Health Levine Cancer Institute
๐บ๐ธCharlotte, North Carolina, United States
UNC Lineberger Comprehensive Cancer Center
๐บ๐ธDurham, North Carolina, United States
UT Southwestern, Harold C. Simmons Comprehensive Cancer Center
๐บ๐ธDallas, Texas, United States
University of Utah, Huntsman Cancer Hospital
๐บ๐ธSalt Lake City, Utah, United States
VCU Medical Center
๐บ๐ธRichmond, Virginia, United States