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Screening to Improve Survival in AL Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04615572
Recruitment Status : Recruiting
First Posted : November 4, 2020
Last Update Posted : October 28, 2021
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Tufts Medical Center

Brief Summary:
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.

Condition or disease
Smoldering Multiple Myeloma Monoclonal Gammopathy of Undetermined Significance

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Screening to Improve Survival in AL Amyloidosis
Actual Study Start Date : August 28, 2020
Estimated Primary Completion Date : August 28, 2022
Estimated Study Completion Date : August 28, 2022

Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

Biospecimen Retention:   Samples With DNA
cDNA derived from bone marrow CD138-selected plasma cells.

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Smoldering Multiple Myeloma or Monoclonal Gammopathy of Undetermined Significance patients.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04615572

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Contact: Raymond Comenzo, MD 617-636-6454
Contact: Denis Toskic, BS 617-636-5907

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United States, California
University of California, Irvine Health Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Blake Johnson   
Principal Investigator: Lisa Lee, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Chloe Ryan    415-514-5059   
Principal Investigator: Sandy Wong, MD         
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center Not yet recruiting
Miami, Florida, United States, 33136
Principal Investigator: James Hoffman, MD         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Denis Toskic, BS    617-636-5907   
Principal Investigator: Raymond Comenzo, MD         
Sub-Investigator: Ping Zhou, MD, PhD         
United States, New York
Columbia University Irving Medical Center Recruiting
New York, New York, United States, 10032
Contact: Niharika Mamillapalli    212-342-3849   
Principal Investigator: Suzanne Lentzsch, MD         
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Nick Mangieri   
Principal Investigator: Sascha Tuchman, MD         
Sponsors and Collaborators
Tufts Medical Center
National Institute on Aging (NIA)

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Responsible Party: Tufts Medical Center Identifier: NCT04615572    
Other Study ID Numbers: 00000858
1R21AG070502-01 ( U.S. NIH Grant/Contract )
First Posted: November 4, 2020    Key Record Dates
Last Update Posted: October 28, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tufts Medical Center:
AL Amyloidosis
Additional relevant MeSH terms:
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Multiple Myeloma
Immunoglobulin Light-chain Amyloidosis
Smoldering Multiple Myeloma
Monoclonal Gammopathy of Undetermined Significance
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Precancerous Conditions