RecruitingNCT04300101

Mixed Molecular Clinical Index (MMCI) in Diffuse Large B-cell Lymphoma (DLBCL)


Sponsor

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

Enrollment

300 participants

Start Date

May 14, 2020

Study Type

OBSERVATIONAL

Conditions

Summary

This is a prospective and retrospective observational study. The primary objective is to identify new prognostic biomarkers for DLBCL patients in terms of progression-free survival (PFS) and able to add predictive capacity to recognized important clinical factors. The secondary objectives are: * to identify new biomarkers associated with overall survival (OS) and objective response rate (ORR) * to characterize tissue and circulating immune microenvironment of DLBCL patients by bulk and single cell transcriptomics; * to assess the correlation between the expression of immune checkpoint genes and mRNA signature; * to describe the mutational status of a panel of genes relevant to DLBCL pathogenesis;. * to assess the correlation between protein expression, mutational status and the messenger RNA (mRNA) signature. * to investigate the association between radiomic features obtained from PET images and patient and tumour characteristics and clinical outcomes (PFS, OS, ORR). For each enrolled patient, immunohistochemical determinations will be performed: Cell of origin (COO) (Germinal Cell -GC- or activated B-cell - ABC- type according with Hans algorithm ), evaluation of cluster of differentiation antigen 20 (CD20), cluster of differentiation antigen 5 (CD5), cluster of differentiation antigen 10 (CD10), Bcl6, Bcl2 (cut off\>50%), Multiple Myeloma 1 / Interferon Regulatory Factor 4 protein (MUM1/IRF4), c-myc (cut off\>40%) and Ki67, fluorescence in situ hybridization (FISH) for c-myc and if rearranged, for Bcl2 e Bcl6 ). Moreover, paraffin embedded (FFPE) tumor specimens will be collected for RNA extraction and mRNA expression mutational and proteomics analysis, centralized at IRST-IRCCS.


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • New diagnosis of High grade Diffuse large B cell Lymphoma undergoing first line standard treatment;
  • Signed written informed consent;
  • Availability of FFPE sample.
  • Diagnosis of High grade Diffuse large B cell Lymphoma from 2011 to 2017;
  • Availability of FFPE sample and clinical data.

Exclusion Criteria1

  • Patients included in clinical trials.

Interventions

OTHERProspective cohort

Immunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis

OTHERRetrospective cohort

Immunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis


Locations(4)

Irst Irccs

Meldola, FC, Italy

Ospedale S. Maria delle Croci RAVENNA

Ravenna, RA, Italy

L'Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola-Malpighi

Bologna, Italy

Ospedale Infermi

Rimini, Italy

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NCT04300101


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