Promoting Diagnosis and Management of AL in Italy (ProDigALIty)

NCT ID: NCT06383143

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 760 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2025-05-01

Brief 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

Detailed 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.

Conditions

AL Amyloidosis; Smoldering Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with MGUS and aFLCR and with SMM

Part A: Patients with MGUS and aFLCR and patients with SMM undergoing an active, biomarker-based screening of presymptomatic amyloid organ involvement.

Part B: Newly diagnosed patients with AL amyloidosis identified through Part A or with clinically overt AL amyloidosis evaluated in the frame of routine clinical assessments and referred to the Amyloidosis Research and Treatment Center in Pavia or managed locally at the participating Italian Hematologic Departments

no intervention

Intervention Type: OTHER

no intervention

Interventions

no intervention

no intervention

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• diagnosis of MGUS with altered FLCR or SMM;
• treatment-naïve;
• age ≥18 years;
• ability to understand and willingness to sign an informed consent;
• planned follow-up at participating center.

• diagnosis of systemic AL amyloidosis;
• treatment-naïve;
• age ≥18 years;
• ability to understand and willingness to sign an informed consent;
• planned follow-up at participating center.

Exclusion Criteria

• Diagnosis of symptomatic monoclonal gammopathies;
• Previous treatment for monoclonal gammopathies.

PART B

• non-AL amyloidosis;
• previous treatment for AL amyloidosis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Palladini

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliera Policlinico Consorziale

Bari, , Italy

Site Status: RECRUITING

Azienda Ospedaliero Universitaria Policlinico G.Rodolico - San Marco

Catania, , Italy

Site Status: RECRUITING

Fondazione Irccs Policlinico San Matteo

Pavia, , Italy

Site Status: RECRUITING

EMATOLOGIA - Città della Scienza e Salute - Torino

Torino, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

PELLEGRINO MUSTO, MD

Role: primary

ematologiacontrapianto@policlinico.ba.it

080 5593471

PELLEGRINO MUSTO, MD

Role: backup

Angela Minervini, MD, PhD

Role: backup

Francesco Di Raimondo, MD

Role: primary

segremat@unict.it

095/378.1956

Francesco Di Raimondo, MD

Role: backup

Concetta Maria Sebastiana Conticello, MD, PhD

Role: backup

GIOVANNI PALLADINI, MD, PhD

Role: primary

segreteria.amiloidosi@smatteo.pv.it

+390382502994

GIOVANNI PALLADINI, MD, PhD

Role: backup

Luca Arcaini, MD

Role: backup

Mario Ulisse Nuvolone, MD, PhD

Role: backup

FRANCESCA MARIA GAY, MD, PhD

Role: primary

ematologia@cittadellasalute.to.it

011.633.5550 - 5935

FRANCESCA MARIA GAY, MD, PhD

Role: backup

Stefania Oliva, MD, PhD

Role: backup

Other Identifiers

AC-020-IT

Identifier Type: -

Identifier Source: org_study_id