Towards Effective, Patient-tailored Anti-plasma Cell Therapies in AL Amyloidosis: Predicting Drug Response and Overcoming Drug Resistance

May 7, 2026 updated by: Mario Nuvolone, Fondazione IRCCS Policlinico San Matteo di Pavia
Through an observational clinical study, partly prospective and partly retrospective, based on the collection of clinical data and on in vitro experimental analyses carried out on residual biological samples obtained during routine clinical procedures, it is proposed to identify predictive biomarkers of in vivo response to first-line therapies.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lombardy
      • Pavia, Lombardy, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Newly diagnosed, treatment naïve AL amyloidosis patients with non-IgM plasma cell clones, evaluated at the amyloidosis Research and Treatment Center of Pavia, undergoing a diagnostic bone marrow aspiration will be enrolled.

Description

Inclusion Criteria:

  • Biopsy-proven systemic AL amyloidosis
  • No IgM clone
  • No history of anti-plasma cell therapy
  • Diagnostic bone marrow aspiration at ARTC
  • Age > 18 years
  • Willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes through signing a written informed consent.

Exclusion Criteria:

  • Non-AL amyloidosis
  • IgM clone
  • Previous anti-plasma cell therapy
  • Age <18 years
  • Failure to show willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of predictive biomarkers of response to proteasome inhibitor-based first-line therapy in AL amyloidosis
Time Frame: From baseline (diagnosis) to 6 months after initiation of first-line therapy
To identify and validate biological, genetic, and proteomic biomarkers predictive of in vivo response to proteasome inhibitor-based first-line therapies in patients with AL amyloidosis. This will be achieved through the integration of ex vivo drug sensitivity assays performed on patient-derived CD138+ plasma cells, characterization of plasma cell and mesenchymal stromal cell biological features, and retrospective and prospective molecular analyses. Biomarker profiles will be correlated with hematologic response at 6 months and used to develop a predictive statistical model of treatment response.
From baseline (diagnosis) to 6 months after initiation of first-line therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Molecular characterization of mechanisms of resistance to proteasome inhibitors
Time Frame: From baseline (diagnosis) to MRD assessment after achievement of complete hematologic response (approximately up to 12-24 months)
To investigate the mutational, transcriptional, and proteomic profiles associated with in vivo resistance to proteasome inhibitors by comparing plasma cell clones at diagnosis and minimal residual disease (MRD). Analyses will include next-generation sequencing, targeted DNA sequencing of genes involved in proteostasis, and quantitative proteomics to identify molecular determinants of drug resistance.
From baseline (diagnosis) to MRD assessment after achievement of complete hematologic response (approximately up to 12-24 months)
Evaluation of the therapeutic potential of deubiquitinating enzyme (DUB) inhibitors
Time Frame: At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
To assess the ex vivo sensitivity of patient-derived amyloidogenic plasma cells to DUB inhibitors and to characterize the expression of DUB family members at RNA and protein level. The study will evaluate whether DUB inhibition can overcome resistance to proteasome inhibitors and identify candidate DUB inhibitors for therapeutic development.
At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
Role of mesenchymal stromal cells in modulating drug response
Time Frame: At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
To evaluate the contribution of patient-derived mesenchymal stromal cells to resistance against proteasome inhibitors by assessing their protective effect in co-culture systems with amyloidogenic plasma cells or cell lines.
At baseline (sample collection at diagnosis) and during ex vivo experimental analyses

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2022

Primary Completion (Actual)

March 30, 2026

Study Completion (Actual)

March 30, 2026

Study Registration Dates

First Submitted

May 7, 2026

First Submitted That Met QC Criteria

May 7, 2026

First Posted (Actual)

May 13, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P_52345_2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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