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A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early (SAVE)

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ClinicalTrials.gov Identifier: NCT02741999
Recruitment Status : Recruiting
First Posted : April 18, 2016
Last Update Posted : September 21, 2017
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center

Brief Summary:
This protocol seeks to enroll smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significant (MGUS) patients with λ light chain (LC) involvement, a group of patients for whom standard of care is observation not treatment. Patients with SMM and MGUS have a precursor plasma cell disorder from which light chain amyloidosis (AL) can evolve. In this trial, enrolled subjects will have blood and if available bone marrow cells evaluated by molecular testing to determine their clonal λ LC variable region (VL) germline gene. Seventy percent of AL cases involve just 7 germline donors, 5 of which are λ germline donors. The hypothesis that will be tested with this protocol is that the presence of AL germline genes associated with AL in patients with a pre-existing diagnosis of λ SMM or λ MGUS indicates the presence of AL or risk of progression to AL.

Condition or disease
Plasma Cell Dyscrasia Monoclonal Gammopathy

Detailed Description:

In this trial up to 200 patients with either λ light chain (LC) monoclonal gammopathy of undetermined significance (MGUS) or λ LC smoldering multiple myeloma (SMM) with a κ::λ LC ratio < 0.26 and whose λ minus κ LC difference (dFLC) is greater than 23 mg/L will be recruited. Heavy chain type will not affect patient eligibility as long as the involved LC is λ type.

Patients may learn about the trial through internet advertisements and contact the data manager to receive the study's enrollment documents. Patient recruitment will be open to all eligible patient within the United States. Informed consent may be obtained in person or by phone. After the patient has completed a HIPPA release form, the patient's physician will be contacted and informed of the patient's consent to this study and will be asked to provide medical records for screening. If the patient is found eligible, the patient and physician will be informed of the required samples for the protocol, which include peripheral blood and marrow aspirate, if available, with both taken during routine clinical procedures. Prepaid FedEx boxes will be provided by the study to ship research samples to Tufts Medical Center for remote patients.

Both the peripheral blood and marrow samples will be tested for the presence of variable region (VL) germline genes in our Tufts Medical Center laboratory. In addition, plasma isolated from the peripheral blood sample (as well as the corresponding identified germline gene) will be sent to the laboratory of Dr. Jonathan Wall at the University of Tennessee for assay analysis. The assay will seek to distinguish the presence of amyloidogenic vs. non-amyloidogenic light chains. Germline gene results from Tufts Medical Center will be shared with patients and their physicians; however, University of Tennessee assay analysis will not be shared due to its experimental nature.

The analysis of this trial will be based on the frequency with which enrolled MGUS and SMM patients are found to have genes associated with light chain amyloidosis (AL), are found to have asymptomatic AL or symptomatic AL, or progress to AL. The diagnosis of AL is a tissue diagnosis. If amyloidosis is suspected at any time during a subject's participation, their physician will be contacted and given recommendations regarding diagnostic tests and disease staging.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early
Study Start Date : April 2016
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023





Primary Outcome Measures :
  1. Observation of disease progression in participants with AL-associated VL germline genes [ Time Frame: 5 years ]
    After sequencing of their light chain (LC) variable region (VL) germline gene, subjects with light chain amyloidosis (AL) associated sequences will be followed for up to 5 years to monitor the potential progression of their disease to AL amyloidosis.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This study will enroll up to 200 MGUS and SMM patients with λ LC involvement with dFLC >23 mg/L and κ:: λ free LC ratio <0.26. Subjects must be able to share their medical records and ship bone marrow and blood samples to our laboratory.
Criteria

Inclusion Criteria:

  • MGUS and SMM patients with λ LC involvement with dFLC > 23 mg/L and κ:: λ free LC ratios < 0.26. Subjects must be able to share their medical records and ship us bone marrow and blood samples.

Exclusion Criteria:

  • MGUS and SMM patients with light chains that do not meet the inclusion criteria as well as patients with κ LC involvement or active myeloma will not be included. And patients who are unable to send us blood and marrow for any reason will not be 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 ClinicalTrials.gov identifier (NCT number): NCT02741999


Contacts
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Contact: Raymond Comenzo, MD 617-636-6454 rcomenzo@tuftsmedicalcenter.org
Contact: Melissa Warner, BS 617-636-5907 mwarner@tuftsmedicalcenter.org

Locations
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United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Melissa T Warner, BS    617-636-5907    mwarner@tuftsmedicalcenter.org   
Contact: Denis Toskic, BS    617-636-5907    dtoskic@tuftsmedicalcenter.org   
Sponsors and Collaborators
Tufts Medical Center
Investigators
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Principal Investigator: Raymond Comenzo, MD Tufts Medical Center

Publications:

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Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT02741999     History of Changes
Other Study ID Numbers: 12016
First Posted: April 18, 2016    Key Record Dates
Last Update Posted: September 21, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
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Amyloidosis
Paraproteinemias
Monoclonal Gammopathy of Undetermined Significance
Immunoglobulin Light-chain Amyloidosis
Multiple Myeloma
Neoplasms, Plasma Cell
Proteostasis Deficiencies
Metabolic Diseases
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hypergammaglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders