Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial
- Conditions
- Follicular Lymphoma
- Interventions
- Diagnostic Test: EZH2 mutations/CNAs by droplet digital PCR (ddPCR)Diagnostic Test: EZH2-derived gene expression signature by RNA-Seq
- Registration Number
- NCT05816850
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 654
- 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);
- None
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients enrolled EZH2-derived gene expression signature by RNA-Seq Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial Patients enrolled EZH2 mutations/CNAs by droplet digital PCR (ddPCR) Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial
- Primary Outcome Measures
Name Time Method Progression free survival From treatment start up to 43 months Time between the treatment start and the first documentation of recurrence, progression or death from any cause
- Secondary Outcome Measures
Name Time Method Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature Before treatment start Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
Response rate 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.
Trial Locations
- Locations (26)
A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
🇮🇹Alessandria, Italy
Nuovo Ospedale degli Infermi, SSD Ematologia
🇮🇹Biella, Italy
ASST Spedali Civili di Brescia - Ematologia
🇮🇹Brescia, Italy
Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
🇮🇹Catania, Italy
A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
🇮🇹Cuneo, Italy
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
🇮🇹Firenze, Italy
Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Ematologia e terapie cellulari
🇮🇹Genova, Italy
IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L., Ematologia
🇮🇹Meldola, Italy
ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
🇮🇹Milano, Italy
Azienda Ospedaliero-Universitaria Policlinico di Modena, U.O. Oncologia
🇮🇹Modena, Italy
Fondazione IRCCS San Gerardo dei Tintori - Ematologia
🇮🇹Monza, Italy
AOU Maggiore della Carità di Novara, SCDU Ematologia
🇮🇹Novara, Italy
Presidio ospedaliero "A. Tortora", U.O. Onco-ematologia
🇮🇹Pagani, Italy
A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
🇮🇹Palermo, Italy
IRCCS Policlinico S. Matteo di Pavia, Divisione di Ematologia
🇮🇹Pavia, Italy
Ospedale Guglielmo da Saliceto, U.O. Ematologia
🇮🇹Piacenza, Italy
Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Ematologia
🇮🇹Reggio Calabria, Italy
Ospedale degli Infermi di Rimini, U.O. di Ematologia
🇮🇹Rimini, Italy
Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
🇮🇹Roma, Italy
Istituto Clinico Humanitas, U.O. Ematologia
🇮🇹Rozzano, Italy
A.O.U. Città della Salute e della Scienza di Torino, Ematologia Universitaria
🇮🇹Torino, Italy
A.O.U. Città della Salute e della Scienza di Torino, S.C. Ematologia
🇮🇹Torino, Italy
A.O. C. Panico, U.O.C Ematologia e Trapianto
🇮🇹Tricase, Italy
Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologica
🇮🇹Udine, Italy
Ospedale di Circolo - U.O.C Ematologia
🇮🇹Varese, Italy