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ClinicalTrials.gov ID

NCT05746858

Lead Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCSOTHER

Overall Status

Not yet recruiting

Study Type

Observational

Enrollment

300Estimated

Last Update Posted

Feb 28, 2023Actual

Start Date

Apr 1, 2023Estimated

Primary Completion Date

Mar 31, 2025Estimated

Completion Date

Mar 31, 2027Estimated

Official Title

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)

Brief Summary

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

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.

• Diffuse Large B Cell Lymphoma
• Relapsed Non-Hodgkin Lymphoma

• no intervention (observational study)

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Observational Model

Cohort

Time Perspective

Other

Lead Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCSOTHER

Collaborators

Istituti Fisioterapici OspitalieriOTHER

Istituto Nazionale Tumori IRCCS - Fondazione G. PascaleNETWORK

stefan.hohaus@unicatt.it