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Immune Profiling in Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT04135079
Recruitment Status : Recruiting
First Posted : October 22, 2019
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Mario Boccadoro, University of Turin, Italy

Brief Summary:
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.

Condition or disease
Multiple Myeloma

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

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Other
Time Perspective: Other
Official Title: Immune Profiling in Multiple Myeloma
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
newly diagnosed, and/or refractory MM patients and healthy donors
Criteria

Inclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04135079


Contacts
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Contact: UNITO UNITO 0116336107 clinical.trials@unito.it

Locations
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Italy
Aou Citta' Della Salute E Della Scienza Di Torino Recruiting
Torino, TO, Italy, 10126
Sponsors and Collaborators
Mario Boccadoro
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Responsible Party: Mario Boccadoro, Principal Investigator, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT04135079    
Other Study ID Numbers: IMMUNE-UNITO
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mario Boccadoro, University of Turin, Italy:
immune transcriptome profile
Drop-seq
immune signatures
CyTOF
cytokine profile
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases