Trial Title:
Predictive Biomarkers Including miRNA-based Tumor Signatures in Diffuse Large B Cell Lymphoma (R/R DLBCL) (MIMOSA)
NCT ID:
NCT05746858
Condition:
Diffuse Large B Cell Lymphoma
Relapsed Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Conditions: Keywords:
miRNA
flow cytometry
next generation sequencing
Study type:
Observational
Overall status:
Not yet recruiting
Study design:
Time perspective:
Other
Intervention:
Intervention type:
Other
Intervention name:
no intervention (observational study)
Description:
No intervention (observational study)
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.
Criteria for eligibility:
Study pop:
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).
Sampling method:
Non-Probability Sample
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Istituto Nazionale Tumori Fondazione "G. Pascale" IRCCS
Address:
City:
Napoli
Country:
Italy
Contact:
Last name:
Antonello Pinto, MD
Email:
a.pinto@istitutotumori.na.it
Contact backup:
Last name:
Mariangela Saggese
Email:
m.saggese@istitutotumori.na.it
Investigator:
Last name:
Rosaria De Filippi, MD
Email:
Sub-Investigator
Investigator:
Last name:
Umberto Falcone, MD
Email:
Sub-Investigator
Investigator:
Last name:
Francesco Volzone, MD
Email:
Sub-Investigator
Facility:
Name:
Fonadazione Policlinico Universitario A. Gemelli
Address:
City:
Roma
Country:
Italy
Contact:
Last name:
Stefan Hohaus, MD
Email:
stefan.hohaus@unicatt.it
Contact backup:
Last name:
Arianna Errico
Email:
errico.arianna@gmail.com
Investigator:
Last name:
Silvia Bellesi, MD
Email:
Sub-Investigator
Investigator:
Last name:
Elena Maiolo, MD
Email:
Sub-Investigator
Investigator:
Last name:
Flaminia Bellisario, MD
Email:
Sub-Investigator
Investigator:
Last name:
Francesco D'Alò, MD
Email:
Sub-Investigator
Facility:
Name:
Istituti Fisioterapici Ospitalieri -Istituto Regina Elena
Address:
City:
Roma
Country:
Italy
Contact:
Last name:
Maria Rizzo, MD
Email:
maria.rizzo@ifo.it
Contact backup:
Last name:
Elena Papa
Email:
ematologia@ifo.it
Investigator:
Last name:
Francesco Marchesi, MD
Email:
Sub-Investigator
Investigator:
Last name:
Giulia Regazzi, PhD
Email:
Sub-Investigator
Start date:
April 1, 2023
Completion date:
March 31, 2027
Lead sponsor:
Agency:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Agency class:
Other
Collaborator:
Agency:
Istituti Fisioterapici Ospitalieri
Agency class:
Other
Collaborator:
Agency:
Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
Agency class:
Other
Source:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05746858
