Clinical trial NCT06588205: Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Keywords: Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
MYC
BCL2
BCL6
Double Hit
Triple Hit
lymphoma micro-environment
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary outcomes:
measure: Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Identify putative prognostic and predictive biomarkers related to the lymphoma microenvironment
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Analyze the impact of the type of therapy, standard or intensified (with or without autotransplantation), on the outcome in the different subgroups of patients
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Assess the risk of central nervous system (CNS) recurrence and the impact of prophylaxis performed with intrathecal chemotherapy vs methotrexate intravenous
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O.U. SS. Antonio e Biagio e C. Arrigo - S.C.D.U. Ematologia
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti delle Marche - Clinica di Ematologia
city: Bari
country: Italy
facility: I.R.C.C.S. Istituto Tumori Giovanni Paolo II - U.O.C. Ematologia
city: Brescia
country: Italy
facility: ASST Spedali Civili - S.C. Ematologia
city: Candiolo
country: Italy
facility: I.R.C.C.S. Istituto di Candiolo - FPO
city: Castelfranco Veneto
country: Italy
facility: I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncoematologia
city: Catania
country: Italy
facility: ARNAS Garibaldi - U.O.C. Ematologia
city: Civitanova Marche
country: Italy
facility: A.S.T. Macerata - U.O.S.D Ematologia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico Fondazione IRCCS Ca' Granda - S.C. Ematologia
city: Padova
country: Italy
facility: A.O.U. di Padova - U.O.C. Ematologia
city: Padova
country: Italy
facility: I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncologia 1
city: Siena
country: Italy
facility: U.O.C. Ematologia - A.O.U. Senese
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia U
city: Treviso
country: Italy
facility: ULSS 2 Ospedale Ca' Foncello - U.O.C. Ematologia
city: Tricase
country: Italy
facility: A.O. Cardinale "G. Panico" - U.O.C Ematologia e Trapianto Midollo Osseo
city: Trieste
country: Italy
facility: A.S.U. Giuliano Isontina - S.C. Ematologia
city: Verona
country: Italy
facility: A.O.U.I. di Verona - Ematologia
Study officials:
affiliation: SC Anatomia Patologica - ASST Spedali Civili di Brescia
name: Luisa Lorenzi, MD
role: PRINCIPAL_INVESTIGATOR
References: