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

NCT ID: NCT05746858

Last Updated: 2023-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-04-01

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diffuse Large B Cell Lymphoma Relapsed Non-Hodgkin Lymphoma

Keywords

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miRNA flow cytometry next generation sequencing

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Interventions

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no intervention (observational study)

No intervention (observational study)

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Istituti Fisioterapici Ospitalieri

OTHER

Sponsor Role collaborator

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

NETWORK

Sponsor Role collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stefan Hohaus, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli

Locations

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Istituto Nazionale Tumori Fondazione "G. Pascale" IRCCS

Napoli, , Italy

Site Status

Fonadazione Policlinico Universitario A. Gemelli

Roma, , Italy

Site Status

Istituti Fisioterapici Ospitalieri -Istituto Regina Elena

Roma, , Italy

Site Status

Countries

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Italy

Central Contacts

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Stefan Hohaus, MD

Role: CONTACT

Phone: 06-30154180

Email: [email protected]

Facility Contacts

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Antonello Pinto, MD

Role: primary

Mariangela Saggese

Role: backup

Stefan Hohaus, MD

Role: primary

Arianna Errico

Role: backup

Maria Rizzo, MD

Role: primary

Elena Papa

Role: backup

Other Identifiers

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ID-5444

Identifier Type: -

Identifier Source: org_study_id