Clinical trial NCT04135079: Immune Profiling in Multiple Myeloma
Official title: Immune Profiling in Multiple Myeloma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Myeloma
Keywords: immune transcriptome profile
Drop-seq
immune signatures
CyTOF
cytokine profile
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2019-10-22
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: newly diagnosed, and/or refractory MM patients and healthy donors

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Determine the immune transcriptome profile in the peripheral blood of MM patients at diagnosis and relapse by bulk and single cell RNAseq.
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: Determine the immune signatures in the peripheral blood of MM patients at diagnosis and relapse by time-of-flight mass cytometry (CyTOF).
timeFrame: through study completion, an average of 2 years
Other outcomes:
measure: Evaluate the cytokine profile in the peripheral blood of MM patients at diagnosis and relapse by cytokine arrays.
timeFrame: through study completion, an average of 2 years
Locations:
city: Torino
country: Italy
facility: Aou Citta' Della Salute E Della Scienza Di Torino
state: TO
Study officials:
affiliation: S.C. Ematologia U
name: Alessandra Larocca
role: PRINCIPAL_INVESTIGATOR
References: