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

NCT07585331 | Completed

• 1 other identifier: P_52345_2019
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Identification of predictive biomarkers of response to proteasome inhibitor-based first-line therapy in AL amyloidosis

  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 Outcomes (3)

• Molecular characterization of mechanisms of resistance to proteasome inhibitors

  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

  At baseline (sample collection at diagnosis) and during ex vivo experimental analyses

• Role of mesenchymal stromal cells in modulating drug response

  At baseline (sample collection at diagnosis) and during ex vivo experimental analyses

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 13, 2026
• Study Start: January 13, 2022
• Primary Completion: March 30, 2026
• Study Completion: March 30, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)