Follicular Lymphoma
Conditions
Keywords
Lymphoma, Follicular, Immunochemotherapy, FL, Aberration, Mutation, EZH2, CHOP, Bendamustine, Biological, Rituximab, Biomarker
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.
Interventions
DIAGNOSTIC_TESTEZH2 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_TESTEZH2-derived gene expression signature by RNA-Seq
Test of EZH2-derived gene expression signature by RNA-Seq in a subset of diagnostic FFPE samples
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
Italy
Contacts
Primary ContactUffici Studi FIL
Backup ContactUffici Studi FIL
Outcome results
None listed