Clinical trial · Observational
Genomic and Phenotypic Determinants of Resistance to Immunotherapies in Multiple Myeloma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Multiple Myeloma | Multiple Myeloma | CURATED_EXACT | 0.92 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Evaluation of patients resistance to immunotherapies in Multiple Myeloma | Diagnostic Test | — | UNRESOLVED |
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (4)
- measure
- Sensitivity vs resistance to new immunotherapies
- timeFrame
- 5 years
- description
- 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).
- measure
- Cell extrinsic mechanisms of response
- timeFrame
- 5 years
- description
- 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.
- measure
- Biomarkers of response
- timeFrame
- 5 years
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * MM patients at clinical relapse who progressed during PIs or IMiDs-based therapies * Patients assigned to antiCD38-based salvage treatments * Patients with measurable disease Exclusion Criteria: * No criteria
References
Publications (1)
- DERIVEDZiccheddu 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