Diffuse Large B Cell LymphomaMIMOSANCT05746858
Predictive Biomarkers Including miRNA-based Tumor Signatures in Diffuse Large B Cell Lymphoma (R/R DLBCL) (MIMOSA)
An observational study of Diffuse Large B Cell Lymphoma and Relapsed Non-Hodgkin Lymphoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 3 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Relapsed Non-Hodgkin Lymphoma
- How many people
- 300 participants
- Where
- 3 sitesItaly
- Study dates
- 1 Apr 2023to 31 Mar 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy3 sites
Istituto Nazionale Tumori Fondazione "G. Pascale" IRCCS
Naples
Antonello Pinto, MD, a.pinto@istitutotumori.na.it
Mariangela Saggese, m.saggese@istitutotumori.na.it
Fonadazione Policlinico Universitario A. Gemelli
Roma
Stefan Hohaus, MD, stefan.hohaus@unicatt.it
Arianna Errico, errico.arianna@gmail.com
Istituti Fisioterapici Ospitalieri -Istituto Regina Elena
Roma
Maria Rizzo, MD, maria.rizzo@ifo.it
Elena Papa, ematologia@ifo.it
About this study
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)
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:
- To explore associations between expression of target antigens on surface of neoplastic cells of DLBCL patients and response to target therapies
- To identify specific miRNA signatures as predictors of response to upfront and salvage immune-chemotherapies in DLBCL patients.
- 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.
Read the 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.
- Being tested
- no intervention (observational study)
- Keywords
- miRNA, flow cytometry, next generation sequencing
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention (observational study)Other
No intervention (observational study)
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission
Complete remission rates according to miRNA signatures, expression of target antigens, mutational status
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2023
- Study start1 Apr 2023 (estimated)
- Primary completion31 Mar 2025 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Istituti Fisioterapici Ospitalieri, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
- Responsible party
- Sponsor
- Investigators
- Stefan Hohaus, MD, Principal investigator, Fondazione Policlinico Universitario A. Gemelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05746858
- Sponsor's protocol ID
- ID-5444
- Acronym
- MIMOSA
- Status last verified
- Feb 2023
- First submitted
- 17 Feb 2023
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Decision on IPD will be jointly made by investigators at end of study
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05746858
- Acronym / sponsor ID
- MIMOSA / ID-5444
- Keywords
- miRNA, flow cytometry, next generation sequencing
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Istituti Fisioterapici Ospitalieri, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
- Study start
- 1 Apr 2023 (estimated)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 28 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To explore associations between expression of target antigens on surface of neoplastic cells of DLBCL patients and response to target therapies
- To identify specific miRNA signatures as predictors of response to upfront and salvage immune-chemotherapies in DLBCL patients.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no intervention (observational study)No intervention (observational study) | Other | – |
Primary outcome
Complete remission
Time frame: 2 years
Complete remission rates according to miRNA signatures, expression of target antigens, mutational status
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Individual participant dataSharing planned: Undecided. Decision on IPD will be jointly made by investigators at end of study
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A Multicenter, Phase I Study to Evaluate the Feasibility and Safety of Autologous Cytokine-Induced Killer Cells (CIK_D332) in Combination With Tafasitamab and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stefan Hohaus, MD principal investigator
Fondazione Policlinico Universitario A. Gemelli
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diffuse Large B Cell Lymphoma and Relapsed Non-Hodgkin Lymphoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stefan Hohaus, MD (06-30154180, stefan.hohaus@unicatt.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.