Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06383143 |
| Other study ID # |
AC-020-IT |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2023 |
| Est. completion date |
May 1, 2025 |
Study information
| Verified date |
April 2024 |
| Source |
IRCCS Policlinico S. Matteo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The investigators plan to establish a dedicated network of Italian Hematologic Departments
interconnected with the Amyloidosis Research and Treatment Center in Pavia to:
1. Implement a biomarker-based screening strategy to promote early diagnosis of AL
amyloidosis among at-risk patients, including patients with monoclonal gammopathy of
undetermined significance, MGUS, and altered free light chain ratio (aFLCR), and
patients with smoldering multiple myeloma (SMM)
2. Expedite and facilitate patients' referral and their enrollment in ongoing
pre-clinical/clinical studies, also to reflect a broader spectrum of the real-world
population of patients with AL amyloidosis in Italy;
3. Investigate the clinical utility of novel diagnostic technologies, including light chain
sequencing and N-glycosylation analysis
Description:
AL amyloidosis (AL) is a rare, severe protein conformational disease caused by misfolding and
extracellular deposition of patients-specific monoclonal immunoglobulin light chains in form
of amyloid fibrils. This process can affect virtually any body site and result in potentially
fatal organ dysfunction.
In a significant proportion of cases, AL is diagnosed late, when advanced, often irreversible
organ involvement limits therapeutic options and greatly limits survival. Thus, efforts at
promoting early diagnosis are urgently needed.
The presence of a monoclonal protein (M protein) or an abnormally increased concentration of
serum free LCs (FLCs) invariably precedes clinically overt AL amyloidosis by several years.
Moreover, about 95% of patients with AL have an altered FLC ratio (FLCR) at diagnosis. Yet,
AL is often diagnosed late also in patients with known monoclonal gammopathy under
hematological follow-up. Screening of at-risk patients with biomarkers of early amyloid organ
involvement has been advocated, but not largely implemented.
Diagnosis and management of AL patients require access to sophisticated technologies and
expertise available at large tertiary Amyloid Centers. Yet, new models of patients' care are
required to intercept those patients who cannot travel to distant, tertiary centers, in order
to provide state-of-the-art care to all and to be able to analyze and describe the natural
history of the disease in a contemporary, real-world setting.
New molecular features associated with the propensity of light chains to form amyloid are
emerging, but their potential clinical utility is unknown. Building on >30 years-experience
of the Italian Referral Center for Systemic Amyloidoses and leveraging on an already existing
disease registry and a one-of-a-kind biorepository of clinically annotated biological
samples, the study plans to extend and corroborate the activity of the Italian Amyloidosis
Network, through the involvement of large Hematology Departments strategically distributed
across the Country and the establishment of a structured program of patients' referral and
sample/data transfer.
The study will be conducted as follows:
Part A: an active biomarker-based surveillance of pre-symptomatic signs of amyloid organ
involvement in at-risk subjects (patients with MGUS and aFLCR and patients with SMM) will be
implemented in the participating Italian Hematologic Departments. This will enable the
verification of the feasibility of such biomarker-based screening, allow the description of
baseline characteristics of at-risk patients, and promote early diagnosis of AL amyloidosis.
Part B: newly diagnosed AL amyloidosis patients (either from Part A or from patients with
clinically overt AL amyloidosis evaluated in the frame of routine clinical assessments) will
be either referred to the Amyloidosis Research and Treatment Center in Pavia or managed
locally, with clinical data prospectively entering a disease registry and diagnostic
leftovers from biospecimens stored in a biorepository. This will aim to increase referral and
increment inclusion of real-world cases of AL amyloidosis in the disease registry and linked
biorepositories, as well as patients' enrollment in other already approved and funded
pre-clinical and clinical studies on basic disease mechanisms, as well as new
diagnostic/therapeutic approaches in AL amyloidosis.
Part C: exploiting data collected from patients enrolled in both part A and part B, the
clinical utility of clonal light chain profiling (including light chain sequencing,
evaluation of the N-glycosylation status, and artificial intelligence-based amyloidogenicity
prediction) will be assessed.
