Clinical trial NCT05816850: Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial
Official title: Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Follicular Lymphoma
Keywords: Lymphoma
Follicular
Immunochemotherapy
FL
Aberration
Mutation
EZH2
CHOP
Bendamustine
Biological
Rituximab
Biomarker
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2023-04-18
Enrollment: 654
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient affected by advanced Follicular Lymphoma treated with immunochemotherapy in the FIL_FOLL12 trial

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: From treatment start up to 43 months
Secondary outcomes:
measure: Response rate
timeFrame: From treatment start to 7 months (R-Bendamustine) or from treatment start to 5,6 months (R-CHOP)
measure: Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature
timeFrame: Before treatment start
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
city: Biella
country: Italy
facility: Nuovo Ospedale degli Infermi, SSD Ematologia
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia - Ematologia
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
city: Cuneo
country: Italy
facility: A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Ematologia e terapie cellulari
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L., Ematologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena, U.O. Oncologia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori - Ematologia
city: Novara
country: Italy
facility: AOU Maggiore della Carità di Novara, SCDU Ematologia
city: Pagani
country: Italy
facility: Presidio ospedaliero "A. Tortora", U.O. Onco-ematologia
city: Palermo
country: Italy
facility: A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo di Pavia, Divisione di Ematologia
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto, U.O. Ematologia
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Ematologia
city: Rimini
country: Italy
facility: Ospedale degli Infermi di Rimini, U.O. di Ematologia
city: Roma
country: Italy
facility: Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas, U.O. Ematologia
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino, Ematologia Universitaria
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino, S.C. Ematologia
city: Tricase
country: Italy
facility: A.O. C. Panico, U.O.C Ematologia e Trapianto
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologica
city: Varese
country: Italy
facility: Ospedale di Circolo - U.O.C Ematologia
Study officials:
affiliation: SC Ematologia U - AOU Città della Salute e della Scienza di Torino
name: Simone Ferrero, MD
role: PRINCIPAL_INVESTIGATOR
References: