Immune Profiling in Multiple Myeloma

January 15, 2025 updated by: Mario Boccadoro
This study propose to investigate the immune repertoire of MM patients at the time of diagnosis vs. 1st vs. 2nd vs. 3rd relapse. This study will provide insights into the immune status of MM patients before and after disease transformation and help identify patients who will benefit from immunotherapy. It will also allow us to predict the efficacy of these immune-mediated strategies and their associated toxicity. By understanding the immune-microenvironment in MM patients during disease progression, the investigator will be able to better design immunotherapeutic strategies for maximal success.

Study Overview

Status

Completed

Conditions

Detailed Description

Background: Immunotherapy has emerged as a new therapeutic strategy for the treatment of multiple myeloma (MM). The current immune-based strategies include the FDA-approved monoclonal antibodies elotuzumab1 and daratumumab2 targeting SLAMF7 and CD38 respectively, as well as immune approaches undergoing active clinical investigations such as bispecific T-cell engager,3 antibody-drug conjugate4 and cellular therapies like chimeric antigen receptor T cells.5-7 All of these treatment strategies are currently being tested in relapsed and refractory MM. However, MM patients, particularly those in the later stage of the disease, often have an impaired immune system.8-13 Given their curative potential, the investigator believe that immunotherapies should be used up front when the patient's immune system is still capable of mounting a normal immune response. Here the investigator propose to investigate the immune repertoire of MM patients at the time of diagnosis vs. 1st vs. 2nd vs. 3rd relapse. This study will provide insights into the immune status of MM patients before and after disease transformation and help identify patients who will benefit from immunotherapy. It will also allow us to predict the efficacy of these immune-mediated strategies and their associated toxicity. By understanding the immune-microenvironment in MM patients during disease progression, the investigator will be able to better design immunotherapeutic strategies for maximal success.

Samples: Peripheral blood samples from 20 newly diagnosed, 20 relapsed and/or refractory MM patients and 10 healthy donors will be collected before therapy. An additional peripheral blood sample will be collected at relapse in patients experiencing an early relapse (within 12 months from the start of therapy).

The project will include both a retrospective collection and a prospective collection of samples. Samples will be used for the current study after informed consent from the patient. The samples will be processed by Ficoll Paque gradient to isolate peripheral blood mononuclear cells (PBMCs). Peripheral blood serum will be collected as well.

Enrollment time: 9 months

Study Type

Observational

Enrollment (Actual)

50

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
    • TO
      • Torino, TO, Italy, 10126
        • Aou Citta' Della Salute E Della Scienza Di Torino

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

newly diagnosed, and/or refractory MM patients and healthy donors

Description

Inclusion Criteria:

  • newly diagnosed MM patients or
  • refractory MM patients or
  • healthy donors.

Esclusion criteria:

  • not newly diagnosed MM patients or
  • not refractory MM patients or
  • no healthy donors.

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

  • Observational Models: Other
  • Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the immune transcriptome profile in the peripheral blood of MM patients at diagnosis and relapse by bulk and single cell RNAseq.
Time Frame: through study completion, an average of 2 years
PBMC samples will be subjected to bulk and single cell RNA sequencing for a comprehensive analysis of their immune transcriptomes, including but not limited to the gene expression profiles of high-resolution subsets of B cell, T cell, NK cell and myeloid compartments.
through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the immune signatures in the peripheral blood of MM patients at diagnosis and relapse by time-of-flight mass cytometry (CyTOF).
Time Frame: through study completion, an average of 2 years
PBMCs will be subjected to CyTOF14, 15 for detailed immune cell analysis. All the major immune cell compartments including subsets of B cells, T cells, NK cells and myeloid cells will be assessed for their potential prognostic relevance in disease progression.
through study completion, an average of 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the cytokine profile in the peripheral blood of MM patients at diagnosis and relapse by cytokine arrays.
Time Frame: through study completion, an average of 2 years
Peripheral blood serum will be subjected to cytokine arrays16 to screen for biomarkers that may predict potential adverse effects such as a cytokine storm. This cytokine profiling can potentially be used as a predictor of therapy-induced immune response, and thereby a treatment response. The cytokines that will be assessed are: 4-1BB, 4-1BB ligand, APRIL, B7-1, B7-2, B7-H1, B7-H2, BAFF, BCMA, CD27, CD40, CD40L, Fas, Fas L, Ferritin, GM-CSF, HVEM, ICOS, IFNg, IL10, IL12p40, IL12p70, IL-15, IL-17, IL-1b, IL-2, IL-2 Ra, IL-2 Rg, IL-4, IL-5, IL-6, IL-7, IL-8, L-selectin, MIP-1a, PD-1, PECAM-1, TGFb1, TIM-3, TNFa
through study completion, an average of 2 years

Collaborators and Investigators

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

Sponsor

Mario Boccadoro

Investigators

  • Principal Investigator: Alessandra Larocca, S.C. Ematologia U

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)

April 15, 2019

Primary Completion (Actual)

April 28, 2021

Study Completion (Actual)

December 16, 2024

Study Registration Dates

First Submitted

July 4, 2019

First Submitted That Met QC Criteria

October 21, 2019

First Posted (Actual)

October 22, 2019

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 15, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMMUNE-UNITO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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