Screening to Improve Survival in AL Amyloidosis

Study Overview
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Brief Summary
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The purpose of this study is to see whether certain genes may be linked with the development of AL amyloidosis in subjects 60 years of age or older with the blood disorders SMM and MGUS. A limited repertoire of immunoglobulin (Ig) variable region genes have been associated with AL amyloidosis. The clonal plasma cells of subjects with SMM and MGUS may express one of these Ig variable region genes indicating a risk of progression to AL amyloidosis and potentially enabling early diagnosis. We hope this study will help us begin to understand whether Ig variable region gene identification can be a useful tool for assessing a subject's risk of progression to AL amyloidosis.

Official Title
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Screening to Improve Survival in AL Amyloidosis

Conditions
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Smoldering Multiple Myeloma, Monoclonal Gammopathy of Undetermined Significance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 60 years of age and older Diagnosed with λ LC MGUS or λ LC SMM dFLC greater than 23 mg/L and κ::λ free LC ratio below normal If the patient has an eGFR less than 50 mL/min/1.73m2, the κ::λ free LC ratio is inconsequential. The patient only needs to meet the age, dFLC, and λ LC MGUS or λ LC SMM diagnosis criteria in this case Exclusion Criteria: Patients with κ LC MGUS or κ LC SMM Amyloid in the bone marrow or in other biopsies will not be included Patients younger than 60 years of age are not eligible

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine risk of AL in patients with λ SMM or λ MGUS | By creating a multicenter network (N =6) we will have study centers in Massachusetts (1), California (2), New York (1), North Carolina (1) and Florida (1), enabling us to evaluate 50 patients 60 or older with λ SMM or λ MGUS and to determine based on gene identification whether their clonal λ IGVL genes are AL-related. This approach will identify undiagnosed patients early in the course of AL and patients at risk for AL. | 2 years | 
| To develop a B-cell Gene Rearrangement (BCGR) test for λ IGVL germline gene identification | Testing for markers such as λ IGVL germline genes is highly complex as defined by the Clinical Laboratory Improvement Act (CLIA) (42 USC 263a). We will continue identifying clonal λ IGVL genes with RT-PCR using cDNA derived from bone marrow CD138-selected plasma cells in our research lab, and have partnered with a CLIA-certified diagnostic laboratory, the Columbia University Laboratory of Personalized Genomic Medicine, in order to develop and validate a next generation sequencing (NGS) approach as a CLIA compliant B-cell Gene Rearrangement Test (BCGR, CPT: 81261). | 2 years | 
| To determine if marrow mononuclear cells are adequate for λ IGVL germline gene identification | The multicenter trial will employ bone marrow aspirate mononuclear cells in two ways. First, a portion of each patient's marrow mononuclear cells will be used directly for cDNA for NGS and a portion used to select CD138+ plasma cells for cDNA for RT-PCR and NGS. The use of cDNA derived from bone marrow aspirate mononuclear cells for NGS would save the step of selection and be more convenient if it is equally informative. Criteria identifying specimens that likely do or do not require CD138-selection may be identified in this process. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SMM, MGUS, AL Amyloidosis