Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial

Follicular Lymphoma Clinical Trial

— FIL_FOLL-BIO  

Official title:

Multilayer Biological Characterization of Advanced Follicular Lymphoma: a Translational Study From FIL_FOLL12 Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05816850
• Other study ID #: FIL_FOLL-BIO
• Status: Recruiting
• Start date: September 19, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: December 2023
• Source: Fondazione Italiana Linfomi - ETS
• Contact: Uffici Studi FIL
• Phone: +390131033153
• Email: startup[@]filinf.it
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 654
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

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
• 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

Locations

Country	Name	City	State
Italy	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

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi - ETS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	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	Response rate	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)
Secondary	Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature	Concordance between EZH2 gene mutations/gains and EZH2-related gene expression signature	Before treatment start