Genomic and Phenotypic Determinants of Resistance to Immunotherapies in Multiple Myeloma

NCT03848676 | Completed

• 1 other identifier: IG-20541
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A total of 40 Multiple Myeloma (MM) patients at clinical relapse who progressed during Proteasome Inhibitors (PIs) or Immunomodulating Drugs (IMiDs)-based therapies and who are assigned to antiCD38-based salvage treatments, will be enrolled. We will collect bone marrow (BM) and peripheral blood (PB) samples from patients at specific timepoints:

• baseline (BM, PB and buccal swab)
• every 3 month (PB)
• achievement of response (≥ Very Good Partial Response (VGPR)) (BM and PB)
• relapse or refractory status to antiCD38-based treatments (BM and PB) Samples will be processed and stored in the "Hematological Laboratory" located in the University of Turin (Italy) for various proposed analyses: at specific time-points CD138+ (Plasma Cells-PCs) and marker CD138/19+ (B cells) will be immunomagnetically enriched from the BM mononuclear cells and frozen as viable cells in dimethyl sulfoxide (DMSO); PB mononuclear cells (PBMCs) will be isolated from whole blood by density-gradient centrifugation, and frozen as above; plasma fraction from PB and BM will be obtained by centrifugation and stored frozen; a buccal swab will be obtained at the time of enrollment as a source of control germline DNA and stored frozen.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Immunotherapies; Genomic; Resistance

Outcome Measures

Primary Outcomes (4)

• Sensitivity vs resistance to new immunotherapies

  The patients' response to new drugs administration will be evaluated identifying genomic aberrations (e.g. TRAF3 deletion/mutation and Cereblon mutation) or impaired cellular surface molecules expression (eg CD38, CD55, CD59 expression).

  5 years

• Cell extrinsic mechanisms of response

  The analysis will include T-cells population (eg. CD38+, CD4+, CD8+, Tregs cells), regulatory and suppressive immune populations (MDSCs) and cytokines (eg Activin-A, IL-3, IL-6, RANKL, OPG, MIP-1α, MIP-3α and DKK-1) characterization.

  5 years

• Biomarkers of response

  Response measured through cytofluorimetric analysis. Results will be integrated by statistical models (e.g. univariate, multivariate analysis) and then correlated to mutational results and patients' available clinical data in order to predict outcome.

  5 years

• Biomarkers of response

  Response measured through mutational analysis. Results will be integrated by statistical models (e.g. univariate, multivariate analysis) and then correlated to cytofluorimetric results and patients' available clinical data in order to predict outcome.

  5 years

Interventions

Evaluation of patients resistance to immunotherapies in Multiple Myeloma DIAGNOSTIC_TEST

There are only collections of the samples.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

MM patients at clinical relapse who progressed during PIs or IMiDs-based therapies and who are assigned to antiCD38-based salvage treatments

You may qualify if:

• MM patients at clinical relapse who progressed during PIs or IMiDs-based therapies
• Patients assigned to antiCD38-based salvage treatments
• Patients with measurable disease

You may not qualify if:

• No criteria

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

Dipartimento di Biotecnologie Molecolari e Scienze per la Salute

Torino, TO, 10126, Italy

Location

Related Publications (1)

• Ziccheddu B, Giannotta C, D'Agostino M, Bertuglia G, Saraci E, Oliva S, Genuardi E, Papadimitriou M, Diamond B, Corradini P, Coffey D, Landgren O, Bolli N, Bruno B, Boccadoro M, Massaia M, Maura F, Larocca A. Genomic and immune determinants of resistance to daratumumab-based therapy in relapsed refractory multiple myeloma. Blood Cancer J. 2024 Jul 19;14(1):117. doi: 10.1038/s41408-024-01096-6.

  PMID: 39030183 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood and bone marrow.

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: February 21, 2019
• Study Start: July 1, 2018
• Primary Completion: July 1, 2024
• Study Completion: December 10, 2024
• Last Updated: December 11, 2024

Record last verified: 2024-12

Locations

IT (1)