Follicular LymphomaFIL_FOLL-BIONCT05816850
Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial
An observational study of Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 26 sites in Italy.
Trial summary
This is a Multicenter, Retrospective, Biological study ancillary to FOLL12 trial to evaluate the role of EZH2 aberrations in patient with FL treated with immunochemotherapy. Moreover, several novel biomarkers of FL will be investigated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma
- What is being tested?
- EZH2 mutations/CNAs by droplet digital PCR (ddPCR) and EZH2-derived gene expression signature by RNA-Seq
- How many people
- 654 participants
- Where
- 26 sitesItaly
- Study dates
- 19 Sep 2023to 1 Jun 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: Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial
Who may be able to join
- Patient enrolled in the FIL_FOLL12 trial (documented by the signature of the study informed consent);
- Availability of biological samples: bone marrow aspirate, peripheral blood and/or FFPE diagnostic sample (nodal or extranodal);
Who cannot join
- None
Trial locations and contacts
26 sites in 1 country. Contact the study team or a site near you to ask about taking part.
26 sites in 1 country
Italy26 sites, 26 recruiting
- Recruiting
A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
Alessandria
Manuela Zanni, MD, manuela.zanni@ospedale.al.it
Manuela Zanni, MD
- Recruiting
Nuovo Ospedale degli Infermi, SSD Ematologia
Biella
Annarita Conconi, MD, annarita.conconi@aslbi.piemonte.it
Annarita Conconi, MD
- Recruiting
ASST Spedali Civili di Brescia - Ematologia
Brescia
Antonella Anastasia, MD, antonella.anastasia@gmail.com
Antonella Anastasia, MD
- Recruiting
Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
Catania
Annalisa Chiarenza, MD, annalisa.chiarenza@gmail.com
Annalisa Chiarenza, MD
- Not yet recruiting
A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
Cuneo
Claudia Castellino, MD, castellino.c@ospedale.cuneo.it
Claudia Castellino, MD
- Not yet recruiting
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
Florence
Benedetta Puccini, MD, puccinib@aou-careggi.toscana.it
Benedetta Puccini, MD
- Recruiting
Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Ematologia e terapie cellulari
Genova
Chiara Ghiggi, MD, chiara.ghiggi@hsanmartino.it
Chiara Ghiggi, MD
- Recruiting
IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L., Ematologia
Meldola
Gerardo Musuraca, MD, gerardo.musuraca@irst.emr.it
Gerardo Musuraca, MD
- Recruiting
ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia
Milan
Vittorio Ruggero Zilioli, MD, vittorioruggero.zilioli@ospedaleniguarda.it
Vittorio Ruggero Zilioli, MD
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
Milan
Paolo Corradini, MD, paolo.corradini@unimi.it
Paolo Corradini, MD
- Recruiting
Azienda Ospedaliero-Universitaria Policlinico di Modena, U.O. Oncologia
Modena
Alessia Bari, MD, alessia.bari@unimore.it
Alessia Bari, MD
- Recruiting
Fondazione IRCCS San Gerardo dei Tintori - Ematologia
Monza
Silvia Bolis, MD, silviaanna.bolis@irccs-sangerardo.it
Silvia Bolis, MD
- Recruiting
AOU Maggiore della Carità di Novara, SCDU Ematologia
Novara
Riccardo Moia, MD, riccardo.moia@uniupo.it
Riccardo Moia, MD
- Recruiting
Presidio ospedaliero "A. Tortora", U.O. Onco-ematologia
Pagani
Catello Califano, MD, c.califano@aslsalerno.it
Catello Califano, MD
- Recruiting
A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
Palermo
Caterina Patti, MD, k.patti@villasofia.it
Caterina Patti, MD
- Not yet recruiting
IRCCS Policlinico S. Matteo di Pavia, Divisione di Ematologia
Pavia
Luca Arcaini, MD, luca.arcaini@unipv.it
Luca Arcaini, MD
- Recruiting
Ospedale Guglielmo da Saliceto, U.O. Ematologia
Piacenza
Annalisa Arcari, MD, a.arcari@ausl.pc.it
Annalisa Arcari, MD
- Not yet recruiting
Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Ematologia
Reggio Calabria
Caterina Stelitano, MD, caterinastelitano27@gmail.com
Caterina Stelitano, MD
- Not yet recruiting
Ospedale degli Infermi di Rimini, U.O. di Ematologia
Rimini
Melania Celli, MD, melania.celli@auslromagna.it
Melania Celli, MD
- Recruiting
Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
Roma
Ilaria Del Giudice, MD, ilaria.delgiudice@uniroma1.it
Ilaria Del Giudice, MD
- Recruiting
Istituto Clinico Humanitas, U.O. Ematologia
Rozzano
Francesca Ricci, MD, francesca.ricci@humanitas.it
Francesca Ricci, MD
- Recruiting
A.O.U. Città della Salute e della Scienza di Torino, Ematologia Universitaria
Torino
Simone Ferrero, MD, simone.ferrero@unito.it
Simone Ferrero, MD
- Recruiting
A.O.U. Città della Salute e della Scienza di Torino, S.C. Ematologia
Torino
Carola Boccomini, MD, cboccomini@cittadellasalute.to.it
Carola Boccomini, MD
- Not yet recruiting
A.O. C. Panico, U.O.C Ematologia e Trapianto
Tricase
Vincenzo Pavone, MD, salentoematologia@piafondazionepanico.it
Vincenzo Pavone, MD
- Recruiting
Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologica
Udine
Jacopo Olivieri, MD, jacopo.olivieri@asufc.sanita.fvg.it
Jacopo Olivieri, MD
- Not yet recruiting
Ospedale di Circolo - U.O.C Ematologia
Varese
Michele Merli, MD, michele.merli@asst-settelaghi.it
Michele Merli, MD
About this study
This is a Multicenter, Retrospective, Biological study ancillary to FOLL12 trial to evaluate the role of EZH2 aberrations in patient with FL treated with immunochemotherapy. Moreover, several novel biomarkers of FL will be investigated.
Read the detailed description
Current standard first-line treatment for advanced follicular lymphoma (FL) is still represented by chemoimmunotherapy combinations, with CHOP/CVP or bendamustine (B) as the main regimens with no standard criteria to prefer one over another.
EZH2 mutations have been associated with longer progression-free survival (PFS) in patients treated with CHOP/CVP regimens, but not with Bendamustine (independently from the type of anti-CD20 therapy received).
The FIL_FOLL12 trial (NCT02063685), a large phase III trial (with a pre-planned biological material sampling) enrolling 807 advanced FL patients treated with front-line R-CHOP or bendamustine-rituximab (BR), appears an ideal platform to validate the predictive value of EZH2 and its applicability to the clinical practice.
The aim of this study is to provide to clinicians a useful and practical biomarker to guide the choice of the most effective chemotherapy backbone (in addition to anti-CD20 immunotherapy) for first line treatment of patients with advanced FL (e.g. R-CHOP for EZH2 aberrated vs BR for EZH2 wild type patients).
Moreover, to implement an Italian network of laboratories able to provide these translational outputs within a rapid turnaround time.
Finally, taking advantage of the already collected BM and PB samples, several novel biomarkers of FL heterogeneity will be investigated, in particular: EZH2 protein expression in tumor samples, alternative molecular markers for minimal residual disease (MRD), clonal hematopoiesis of indeterminate potential (CHIP), pharmacogenomics and constitutional genomics as well as microbiome profiles.
- Conditions
- Follicular Lymphoma
- Being tested
- EZH2 mutations/CNAs by droplet digital PCR (ddPCR), EZH2-derived gene expression signature by RNA-Seq
- Keywords
- Lymphoma, Follicular, Immunochemotherapy, FL, Aberration, Mutation, EZH2, CHOP, Bendamustine, Biological, Rituximab, Biomarker
- Medical subject headings
- Lymphoma, Follicular, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EZH2 mutations/CNAs by droplet digital PCR (ddPCR)Diagnostic test
Test of EZH2 mutations/CNAs by droplet digital PCR (ddPCR) in peripheral blood and in unsorted bone marrow aspirate samples at enrolment
EZH2-derived gene expression signature by RNA-SeqDiagnostic test
Test of EZH2-derived gene expression signature by RNA-Seq in a subset of diagnostic FFPE samples
| Study group | Role | What they receive |
|---|---|---|
| Patients enrolled | Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial Receives: Diagnostic Test: EZH2 mutations/CNAs by droplet digital PCR (ddPCR); Diagnostic Test: EZH2-derived gene expression signature by RNA-Seq |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Time between the treatment start and the first documentation of recurrence, progression or death from any cause
Measured: From treatment start up to 43 months
Secondary outcomes (2)
Response rate
Response rate (complete metabolic response/minimal residual disease (MRD) negativity) at the end of induction.
Measured: From treatment start to 7 months (R-Bendamustine) or from treatment start to 5,6 months (R-CHOP)
Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
Measured: Before treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start19 Sep 2023
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular 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
- Retrospective
- Enrolment
- 654 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Italiana Linfomi - ETS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simone Ferrero, MD, Principal investigator, SC Ematologia U - AOU Città della Salute e della Scienza di Torino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05816850
- Sponsor's protocol ID
- FIL_FOLL-BIO
- Acronym
- FIL_FOLL-BIO
- Status last verified
- Sep 2025
- First submitted
- 4 Apr 2023
- Last updated
- 29 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial
- ClinicalTrials.gov ID
- NCT05816850
- Acronym / sponsor ID
- FIL_FOLL-BIO / FIL_FOLL-BIO
- Conditions
- Follicular Lymphoma
- Keywords
- Lymphoma, Follicular, Immunochemotherapy, FL, Aberration, Mutation, EZH2, CHOP
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 654 participants (estimated)
- Lead sponsor
- Fondazione Italiana Linfomi - ETSUniversity, hospital or other
- Study start
- 19 Sep 2023 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 18 Apr 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.
This is a Multicenter, Retrospective, Biological study ancillary to FOLL12 trial to evaluate the role of EZH2 aberrations in patient with FL treated with immunochemotherapy. Moreover, several novel biomarkers of FL will be investigated.
Detailed description
Current standard first-line treatment for advanced follicular lymphoma (FL) is still represented by chemoimmunotherapy combinations, with CHOP/CVP or bendamustine (B) as the main regimens with no standard criteria to prefer one over another.
EZH2 mutations have been associated with longer progression-free survival (PFS) in patients treated with CHOP/CVP regimens, but not with Bendamustine (independently from the type of anti-CD20 therapy received).
The FIL_FOLL12 trial (NCT02063685), a large phase III trial (with a pre-planned biological material sampling) enrolling 807 advanced FL patients treated with front-line R-CHOP or bendamustine-rituximab (BR), appears an ideal platform to validate the predictive value of EZH2 and its applicability to the clinical practice.
The aim of this study is to provide to clinicians a useful and practical biomarker to guide the choice of the most effective chemotherapy backbone (in addition to anti-CD20 immunotherapy) for first line treatment of patients with advanced FL (e.g. R-CHOP for EZH2 aberrated vs BR for EZH2 wild type patients).
Moreover, to implement an Italian network of laboratories able to provide these translational outputs within a rapid turnaround time.
Finally, taking advantage of the already collected BM and PB samples, several novel biomarkers of FL heterogeneity will be investigated, in particular: EZH2 protein expression in tumor samples, alternative molecular markers for minimal residual disease (MRD), clonal hematopoiesis of indeterminate potential (CHIP), pharmacogenomics and constitutional genomics as well as microbiome profiles.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients enrolled | – | Diagnostic Test: EZH2 mutations/CNAs by droplet digital PCR (ddPCR), Diagnostic Test: EZH2-derived gene expression signature by RNA-SeqPatient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial
Key inclusion criteria (2 listed)
- Patient enrolled in the FIL_FOLL12 trial (documented by the signature of the study informed consent);
- Availability of biological samples: bone marrow aspirate, peripheral blood and/or FFPE diagnostic sample (nodal or extranodal);
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| EZH2 mutations/CNAs by droplet digital PCR (ddPCR)Test of EZH2 mutations/CNAs by droplet digital PCR (ddPCR) in peripheral blood and in unsorted bone marrow aspirate samples at enrolment | Diagnostic test | Patients enrolled |
| EZH2-derived gene expression signature by RNA-SeqTest of EZH2-derived gene expression signature by RNA-Seq in a subset of diagnostic FFPE samples | Diagnostic test | Patients enrolled |
Primary outcome
Progression free survival
Time frame: From treatment start up to 43 months
Time between the treatment start and the first documentation of recurrence, progression or death from any cause
2 secondary outcomes
Response rate
Time frame: From treatment start to 7 months (R-Bendamustine) or from treatment start to 5,6 months (R-CHOP)
Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
Time frame: Before treatment start
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 29 Dec 2025.
- Individual participant dataSharing planned: Undecided
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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.
Simone Ferrero, MD principal investigator
SC Ematologia U - AOU Città della Salute e della Scienza di Torino
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 26 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 2 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 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 Uffici Studi FIL (+390131033153, startup@filinf.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: From treatment start up to 43 months). 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 29 Dec 2025.