Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial (FIL_FOLL-BIO)

December 22, 2025 updated by: Fondazione Italiana Linfomi - ETS
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

654

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy
        • Recruiting
        • A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Manuela Zanni, MD
      • Biella, Italy
        • Recruiting
        • Nuovo Ospedale degli Infermi, SSD Ematologia
        • Contact:
        • Principal Investigator:
          • Annarita Conconi, MD
      • Brescia, Italy
        • Recruiting
        • ASST Spedali Civili di Brescia - Ematologia
        • Principal Investigator:
          • Antonella Anastasia, MD
        • Contact:
      • Catania, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
        • Contact:
        • Principal Investigator:
          • Annalisa Chiarenza, MD
      • Cuneo, Italy
        • Not yet recruiting
        • A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
        • Contact:
        • Principal Investigator:
          • Claudia Castellino, MD
      • Florence, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
        • Contact:
        • Principal Investigator:
          • Benedetta Puccini, MD
      • Genova, Italy
        • Recruiting
        • Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Ematologia e terapie cellulari
        • Contact:
        • Principal Investigator:
          • Chiara Ghiggi, MD
      • Meldola, Italy
        • Recruiting
        • IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L., Ematologia
        • Contact:
        • Principal Investigator:
          • Gerardo Musuraca, MD
      • Milan, Italy
      • Milan, Italy
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
        • Principal Investigator:
          • Paolo Corradini, MD
        • Contact:
      • Modena, Italy
        • Recruiting
        • Azienda Ospedaliero-Universitaria Policlinico di Modena, U.O. Oncologia
        • Principal Investigator:
          • Alessia Bari, MD
        • Contact:
      • Monza, Italy
      • Novara, Italy
        • Recruiting
        • AOU Maggiore della Carità di Novara, SCDU Ematologia
        • Contact:
        • Principal Investigator:
          • Riccardo Moia, MD
      • Pagani, Italy
        • Recruiting
        • Presidio ospedaliero "A. Tortora", U.O. Onco-ematologia
        • Contact:
        • Principal Investigator:
          • Catello Califano, MD
      • Palermo, Italy
        • Recruiting
        • A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
        • Contact:
        • Principal Investigator:
          • Caterina Patti, MD
      • Pavia, Italy
        • Not yet recruiting
        • IRCCS Policlinico S. Matteo di Pavia, Divisione di Ematologia
        • Contact:
        • Principal Investigator:
          • Luca Arcaini, MD
      • Piacenza, Italy
        • Recruiting
        • Ospedale Guglielmo da Saliceto, U.O. Ematologia
        • Contact:
        • Principal Investigator:
          • Annalisa Arcari, MD
      • Reggio Calabria, Italy
        • Not yet recruiting
        • Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Ematologia
        • Contact:
        • Principal Investigator:
          • Caterina Stelitano, MD
      • Rimini, Italy
        • Not yet recruiting
        • Ospedale degli Infermi di Rimini, U.O. di Ematologia
        • Contact:
        • Principal Investigator:
          • Melania Celli, MD
      • Roma, Italy
        • Recruiting
        • Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
        • Contact:
        • Principal Investigator:
          • Ilaria Del Giudice, MD
      • Rozzano, Italy
        • Recruiting
        • Istituto Clinico Humanitas, U.O. Ematologia
        • Contact:
        • Principal Investigator:
          • Francesca Ricci, MD
      • Torino, Italy
        • Recruiting
        • A.O.U. Città della Salute e della Scienza di Torino, Ematologia Universitaria
        • Principal Investigator:
          • Simone Ferrero, MD
        • Contact:
      • Torino, Italy
        • Recruiting
        • A.O.U. Città della Salute e della Scienza di Torino, S.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Carola Boccomini, MD
      • Tricase, Italy
      • Udine, Italy
        • Recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologica
        • Principal Investigator:
          • Jacopo Olivieri, MD
        • Contact:
      • Varese, Italy
        • Not yet recruiting
        • Ospedale di Circolo - U.O.C Ematologia
        • Principal Investigator:
          • Michele Merli, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial

Description

Inclusion Criteria:

  • 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);

Exclusion Criteria:

  • None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients enrolled
Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial
Diagnostic test: 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: EZH2-derived gene expression signature by RNA-Seq
Test of EZH2-derived gene expression signature by RNA-Seq in a subset of diagnostic FFPE samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From treatment start up to 43 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: From treatment start to 7 months (R-Bendamustine) or from treatment start to 5,6 months (R-CHOP)
Response rate (complete metabolic response/minimal residual disease (MRD) negativity) at the end of induction.
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
Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
Before treatment start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Italiana Linfomi - ETS

Investigators

  • Principal Investigator: Simone Ferrero, MD, SC Ematologia U - AOU Città della Salute e della Scienza di Torino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

April 4, 2023

First Submitted That Met QC Criteria

April 4, 2023

First Posted (Actual)

April 18, 2023

Study Record Updates

Last Update Posted (Actual)

December 29, 2025

Last Update Submitted That Met QC Criteria

December 22, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_FOLL-BIO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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