Predictive Biomarkers Including miRNA-based Tumor Signatures in Diffuse Large B Cell Lymphoma (R/R DLBCL) (MIMOSA) (MIMOSA)

February 17, 2023 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Deciphering the Biology of Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) Subtypes: Identification of Predictive Biomarkers Including miRNA-based Tumor Signatures to Optimize Sequential Treatment Decisions. (MIMOSA)

The goal of this study is to identify biomarkers that will predict outcome to standard and targeted therapies in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The specific aims of the present project are:

  1. To explore associations between expression of target antigens on surface of neoplastic cells of DLBCL patients and response to target therapies
  2. To identify specific miRNA signatures as predictors of response to upfront and salvage immune-chemotherapies in DLBCL patients.
  3. To refine the diagnosis and molecular profiling of DLBCL, and to provide biological information of prognostic relevance in the setting of innovative treatments of patients with DLBCL.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The research activities will be conducted within a project-specific retrospective/ prospective, multicenter, non-interventional study. The study is non-interventional since all patients will be treated according to institutional guidelines for standard clinical practice at each center.

Duration of the study: this is a two-year project, in the first 4 moths the retrospective part of the study will be performed, the accrual of patients for the prospective part will start rom the fourth month and the analysis of the prospective samples will last until the end of the project. The in vitro model will be established during the first year and the in vitro experiments will be performed until the enst of the project. The last months of the study will be dedicated to the statistical analysis of data and to their interpretation.

This project will be developed through the following specific Tasks:

Task 1: To explore associations between expression of target antigens on surface of neoplastic cells of DLBCL patients and response to target therapies A flow cytometric algorithm has been developed to identify an aberrant CD19+ B cell populations suggestive for aggressive B cell lymphoma that consists in the identification of a cell population defined by either the presence of surface immunoglobulin light chain clonality or the absence of light chains expression in combination with increased FSC and SSC physical parameters. These populations will be analysed for expressioe of target antigens.

Task 2: To identify specific miRNA signatures as predictors of response to upfront and salvage immunotherapies in DLBCL patients.

To this end miRNA expression profiling will be performed by Nanostring technology in formalin fixed and paraffin embedded (FFPE) tumor tissue samples collected at diagnosis. The resulting hits will be further analyzed in matched plasma/serum samples to evaluate the potential use of miRNAs as non-invasive biomarkers.

Task 3: To refine the diagnosis and molecular profiling of DLBCL, and to provide biological information of prognostic relevance in the setting of innovative treatments of patients with DLBCL The major aim is to provide the multilevel characterization (nanostring, NGS) of DLBCL cases that are concurrently utilized to develop a miRNA signature predictive of response to upfront and salvage treatments. Cases will be also characterized for structural alterations of MYC, BCL2 and BCL-6 genes (FISH) and for dual MYC/BCL2 protein expression (immunohistochemistry). In addition, information on pathways of immunosurveillance and microenvironmental functions will be generated.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Napoli, Italy
        • Istituto Nazionale Tumori Fondazione "G. Pascale" IRCCS
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Rosaria De Filippi, MD
        • Sub-Investigator:
          • Umberto Falcone, MD
        • Sub-Investigator:
          • Francesco Volzone, MD
      • Roma, Italy
        • Fonadazione Policlinico Universitario A. Gemelli
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Silvia Bellesi, MD
        • Sub-Investigator:
          • Elena Maiolo, MD
        • Sub-Investigator:
          • Flaminia Bellisario, MD
        • Sub-Investigator:
          • Francesco D'Alò, MD
      • Roma, Italy
        • Istituti Fisioterapici Ospitalieri -Istituto Regina Elena
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Francesco Marchesi, MD
        • Sub-Investigator:
          • Giulia Regazzi, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

a) newly diagnosed DLBCL patients treated with: i) standard R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) and DA-EPOCH -R regimens; ii) frontline Pola-R-CHP (Polatuzumab vendotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone) as approved by the European Medicine Agency-CHMP (24.03.2022); b) RR-DLBCL patients receiving salvage treatments including: a) R-Pola-Benda (Rituximab, Polatuzumab vendotin, Bendamustine); b) Lenalidomide-Tafasitamab; c) Anti-CD19 CAR-T cells; d) bispecific antibodies (e.g. Glofitamab).

Description

Inclusion Criteria:

  • Diagnosis of DLBCL and RR-DLBCL;
  • Age>18 years;
  • Eligibility for first-line and/or salvage chemo-immunotherapies as above specified;
  • Measurable and/or evaluable disease (at least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 cm in its longest dimension);
  • No concomitant active cancers or others life-threatening conditions that can compromise chemotherapy treatment;
  • Available FFPE and fresh tumor tissue (excisional biopsy, Tru-cut microhistology);
  • Informed consent to treatment and use of biologic materials for studies related to the present proposal.

Exclusion Criteria:

  • Diagnosis of follicular lymphoma grade 3b, lymphoblastic lymphoma, Burkitt lymphoma or primary mediastinal lymphoma;
  • Age ≤ 18 years;
  • Ineligible for first-line and/or salvage chemo-immunotherapies;
  • No measurable and/or evaluable disease;
  • Patients with concomitant active solid tumors or others clinical conditions that can compromise chemotherapy treatment or negatively influence the prognosis;
  • Known history of HIV seropositive status. HIV testing will be performed at screening

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission
Time Frame: 2 years
Complete remission rates according to miRNA signatures, expression of target antigens, mutational status
2 years

Collaborators and Investigators

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

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Collaborators

Istituti Fisioterapici Ospitalieri
Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

Investigators

  • Principal Investigator: Stefan Hohaus, MD, Fondazione Policlinico Universitario A. Gemelli

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 (Anticipated)

April 1, 2023

Primary Completion (Anticipated)

March 31, 2025

Study Completion (Anticipated)

March 31, 2027

Study Registration Dates

First Submitted

February 17, 2023

First Submitted That Met QC Criteria

February 17, 2023

First Posted (Estimate)

February 28, 2023

Study Record Updates

Last Update Posted (Estimate)

February 28, 2023

Last Update Submitted That Met QC Criteria

February 17, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID-5444

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Decision on IPD will be jointly made by investigators at end of study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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