SAVE: A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early

Sponsor

Tufts Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02741999

Collaborator

(none)

Enrollment

Location

48.1

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

Study Type:

Observational

Actual Enrollment :

20 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early

Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Apr 5, 2020

Actual Study Completion Date :

Apr 5, 2020

Outcome Measures

Primary Outcome Measures

Observation of disease progression in participants with AL-associated VL germline genes [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.