Screening to Improve Survival in AL Amyloidosis

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.

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Key information

Conditions

Smoldering Multiple Myeloma Amyloidosis Blood Protein Disorders Hematologic Diseases Hemic and Lymphatic Diseases Hypergammaglobulinemia Immune System Diseases Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Lymphoproliferative Disorders Metabolic Diseases Monoclonal Gammopathy of Undetermined Significance Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Nutritional and Metabolic Diseases Paraproteinemias Precancerous Conditions Proteostasis Deficiencies

Age range

60 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of California, Irvine Health Chao Family Comprehensive Cancer Center, Orange, California, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

To determine risk of AL in patients with λ SMM or λ MGUS

Time frame: 2 years

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.
To develop a B-cell Gene Rearrangement (BCGR) test for λ IGVL germline gene identification

Time frame: 2 years

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).
To determine if marrow mononuclear cells are adequate for λ IGVL germline gene identification

Time frame: 2 years

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.

Sponsors and collaborators

Lead sponsor

Tufts Medical Center

Other

Collaborators

National Institute on Aging (NIA)

Registry information

Important dates

Study start: 2020
Primary completion: 2023
Study completion: 2023
First posted: Nov 4, 2020
Registry last updated: Oct 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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