Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma (FIL_MIMYC)

Multicenter, Observational, Retrospective-prospective Study Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma

This is a observational, retrospective and prospective study designed to assess the potential correlations between MYC alterations, lymphoma mutational landscape and functional immune contextures in Diffuse Large B-cell Lymphoma or High-Grade B-cell Lymphoma

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Detailed Description

Diffuse large B-cell lymphomas (DLBCL) and high-grade B-cell lymphomas (HGBCL) are a group of heterogeneous diseases representing more than a third of lymphomas in adults. 5-years overall survival of patients affected by DLBCL and HGBCL is around 70-60% and efficient prognostic markers are warranted to improve patients' survival by better tailored therapeutical approaches.

Genetic rearrangements of the MYC gene occur in 5-10% of DLBCL at diagnosis, and the presence of double translocations involving both MYC and BCL2 ("double-hit", DH), associated or not with BCL6 ("triple-hit", TH) translocation, is associated with unfavorable prognostic impact.

Intensification of treatment compared to standard chemotherapy (R-CHOP) appears to reduce the risk of recurrence in patients with DH or TH lymphomas, but a survival advantage has not been demonstrated.

Numerical changes in MYC (gain of copy number, GCN) may also affect the outcome of patients with DLBCL, but their prognostic relevance and the benefit of treatment intensification is still controversial.

Additionally, novel scientific evidence indicates a contribution of lymphoma micro-environment (LME) in disease genomic subtype and patient prognosis.

We aimed this study at investigating potential biological links between MYC aberrations, lymphoma mutational landscape and functional immune contextures in DLBCL and HGBCL.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Uffici Studi FIL; Phone Number: +390131033153; Email: startup@filinf.it
• Study Contact Backup: Name: Uffici Studi FIL; Phone Number: +390599769913; Email: gestionestudi@filinf.it

Study Locations

• Italy
  • Alessandria, Italy
    • Recruiting
    • A.O.U. SS. Antonio e Biagio e C. Arrigo - S.C.D.U. Ematologia
    • Principal Investigator: Manuela Zanni, MD
    • Contact: Manuela Zanni, MD; Phone Number: +390131206156; Email: manuela.zanni@ospedale.al.it
  • Ancona, Italy
    • Recruiting
    • A.O.U. Ospedali Riuniti delle Marche - Clinica di Ematologia
    • Principal Investigator: Guido Gini, MD
    • Contact: Guido Gini, MD; Phone Number: +390715964562; Email: guido.gini@ospedaliriuniti.marche.it
  • Bari, Italy
    • Recruiting
    • I.R.C.C.S. Istituto Tumori Giovanni Paolo II - U.O.C. Ematologia
    • Contact: Sabino Ciavarella, MD; Phone Number: +390805555408; Email: sabinociavarella@yahoo.it
    • Principal Investigator: Sabino Ciavarella, MD
  • Brescia, Italy
    • Recruiting
    • ASST Spedali Civili - S.C. Ematologia
    • Principal Investigator: Chiara Pagani, MD
    • Contact: Chiara Pagani, MD; Phone Number: +390303996269; Email: chiara.pagani@asst-spedalicivili.it
  • Candiolo, Italy
    • Recruiting
    • I.R.C.C.S. Istituto di Candiolo - FPO
    • Contact: Valentina Sangiorgio, MD; Phone Number: +390119933947; Email: fabiola.sangiorgio@gmail.com
    • Principal Investigator: Valentina Sangiorgio, MD
  • Castelfranco Veneto, Italy
    • Not yet recruiting
    • I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncoematologia
    • Contact: Mariella Lo Schirico, MD; Phone Number: +390432732344; Email: mariella.loschirico@iov.veneto.it
    • Principal Investigator: Mariella Lo Schirico, MD
  • Catania, Italy
    • Recruiting
    • ARNAS Garibaldi - U.O.C. Ematologia
    • Principal Investigator: Ugo Consoli, MD
    • Contact: Ugo Consoli, MD; Phone Number: +390957595055; Email: ugo.consoli144@gmail.com
  • Civitanova Marche, Italy
    • Recruiting
    • A.S.T. Macerata - U.O.S.D Ematologia
    • Contact: Caterina Bocci, MD; Phone Number: +3907332572467; Email: cate.bocci@gmail.com
    • Principal Investigator: Caterina Bocci, MD
  • Florence, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
    • Principal Investigator: Benedetta Sordi, MD
    • Contact: Benedetta Sordi, MD; Phone Number: +390557946445; Email: benedetta.sordi@unifi.it
  • Milan, Italy
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
    • Principal Investigator: Emanuele Ravano, MD
    • Contact: Emanuele Ravano, MD; Phone Number: +390264442668; Email: emanuele.ravano@ospedaleniguarda.it
  • Milan, Italy
    • Recruiting
    • Ospedale Maggiore Policlinico Fondazione IRCCS Ca' Granda - S.C. Ematologia
    • Principal Investigator: Francesca Gaia Rossi, MD
    • Contact: Francesca Gaia Rossi, MD; Phone Number: +390255033466; Email: francescagaia.rossi@policlinico.mi.it
  • Padua, Italy
    • Not yet recruiting
    • A.O.U. di Padova - U.O.C. Ematologia
    • Principal Investigator: Greta Scapinello, MD
    • Contact: Greta Scapinello, MD; Phone Number: +390498217809; Email: greta.scapinello@aopd.veneto.it
  • Padua, Italy
    • Not yet recruiting
    • I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncologia 1
    • Principal Investigator: Dario Marino, MD
    • Contact: Dario Marino, MD; Phone Number: +390498215621; Email: dario.marino@iov.veneto.it
  • Sassuolo, Italy
    • Recruiting
    • AUSL Modena sede di Sassuolo - UOSD di Oncologia Area Sud
    • Principal Investigator: Sara Bigliardi, MD
    • Contact: Sara Bigliardi, MD; Phone Number: +390536846162; Email: s.bigliardi@ausl.mo.it
  • Siena, Italy
    • Not yet recruiting
    • U.O.C. Ematologia - A.O.U. Senese
    • Contact: Alberto Fabbri, MD; Email: fabbri7@unisi.it
    • Principal Investigator: Alberto Fabbri, MD
  • Torino, Italy
    • Not yet recruiting
    • A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia U
    • Principal Investigator: Federica Cavallo, MD
    • Contact: Federica Cavallo, MD; Phone Number: +390116334264; Email: f.cavallo@unito.it
  • Treviso, Italy
    • Recruiting
    • ULSS 2 Ospedale Ca' Foncello - U.O.C. Ematologia
    • Principal Investigator: Piero Maria Stefani, MD
    • Contact: Piero Maria Stefani, MD; Phone Number: +390422322221; Email: pieromaria.stefani@aulss2.veneto.it
  • Tricase, Italy
    • Recruiting
    • A.O. Cardinale "G. Panico" - U.O.C Ematologia e Trapianto Midollo Osseo
    • Contact: Anna Mele, MD; Phone Number: +390833773111; Email: sperimentazionicliniche@piafondazionepanico.it
    • Principal Investigator: Anna Mele, MD
  • Trieste, Italy
    • Recruiting
    • A.S.U. Giuliano Isontina - S.C. Ematologia
    • Principal Investigator: Elisa Lucchini, MD
    • Contact: Elisa Lucchini, MD; Phone Number: +390403992677; Email: elisa.lucchini@asugi.sanita.fvg.it
  • Verona, Italy
    • Not yet recruiting
    • A.O.U.I. di Verona - Ematologia
    • Principal Investigator: Francesca Maria Quaglia, MD
    • Contact: Francesca Maria Quaglia, MD; Phone Number: +390458124827; Email: francescamaria.quaglia@aovr.veneto.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient affected by DLBCL or HGBL with MYC alterations treated with standard R-chemotherapy regimens as first line treatment

Description

Inclusion Criteria:

• Diagnosis of nodal and extranodal Diffuse Large B Cell Lymphoma, High Grade B Cell Lymphomas (including low-grade transformed lymphomas; double and triple hit; 11q aberration; not otherwise specified) after 1st January 2019
• Presence of one MYC translocation or gain of copies (GCN: > 3 copies in more than 30% of the nuclei) or amplification evaluated by FISH
• Availability of immunohistochemical analysis of CD10, Bcl6, MUM1, Bcl2, Myc, Ki67
• Have received curative treatment (e.g. R-CHOP, R DA EPOCH, intensified "Burkitt like" chemotherapies) as first-line therapy
• Histological material of adequate size and quality to perform histological review with any additional investigations (immunohistochemistry, FISH and other molecular analysis). A FFPE block must be provided for patient enrollment.
• Age between 18 and 79 years

Exclusion Criteria:

• Primary lymphomas of the central nervous system, plasmablastic lymphoma, Burkitt's lymphoma, primary mediastinal B lymphoma
• Have received palliative treatment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients enrolled; Patient affected by DLBCL or HGBL with MYC alterations treated with standard R-chemotherapy regimens as first line treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the histopathological, genetic, clinical characteristics and outcome of patients with DLBCL or HGBCL with MYC rearrangements or GCN (alone or in association with BCL2 and BCL6) treated with curative intent therapy	Comparison of Progression Free Survival (PFS) according to genetic subgroups with or without intensified treatment	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology	% of patients with presence of MYC, BCL2 and/or BCL6 translocation evaluated by FISH	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology	% of patients with presence of MYC gain of copy (GCN: > 3 copies in more than 30% of the nuclei) evaluated by FISH	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology	% of patient with presence of MYC amplification evaluated by FISH	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Identify putative prognostic and predictive biomarkers related to the lymphoma microenvironment	Correlation between the microenvironment signature and patient Overall Survival (OS)	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Analyze the impact of the type of therapy, standard or intensified (with or without autotransplantation), on the outcome in the different subgroups of patients	Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Assess the risk of central nervous system (CNS) recurrence and the impact of prophylaxis performed with intrathecal chemotherapy vs methotrexate intravenous	Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received	The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi - ETS
• Investigators: Principal Investigator: Luisa Lorenzi, MD, SC Anatomia Patologica - ASST Spedali Civili di Brescia

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 2, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Diffuse Large B Cell Lymphoma; BCL2; MYC; High-grade B-cell Lymphoma; Double Hit; BCL6; Triple Hit; lymphoma micro-environment
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: FIL_MIMYC

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