Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma
- Conditions
- Diffuse Large B Cell LymphomaHigh-grade B-cell LymphomaHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
- Registration Number
- NCT06588205
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- Primary lymphomas of the central nervous system, plasmablastic lymphoma, Burkitt's lymphoma, primary mediastinal B lymphoma
- Have received palliative treatment
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) Comparison of Progression Free Survival (PFS) according to genetic subgroups with or without intensified treatment
- Secondary Outcome Measures
Name Time Method Identify biological relationship between MYC aberration, gene mutations and patterns of immune microenvironment in B-cell lymphomas with DLBCL or high-grade morphology The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) % of patient with presence of MYC amplification evaluated by FISH
Identify putative prognostic and predictive biomarkers related to the lymphoma microenvironment The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) Correlation between the microenvironment signature and patient Overall Survival (OS)
Analyze the impact of the type of therapy, standard or intensified (with or without autotransplantation), on the outcome in the different subgroups of patients The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received
Assess the risk of central nervous system (CNS) recurrence and the impact of prophylaxis performed with intrathecal chemotherapy vs methotrexate intravenous The endpoint will be evaluated from the beginning to the end of the study (up to 36 months) Progression Free Survival comparison in the different subgroups of lymphomas and according to the type of treatment received
Trial Locations
- Locations (19)
U.O.C. Ematologia - A.O.U. Senese
🇮🇹Siena, Italy
A.O.U. SS. Antonio e Biagio e C. Arrigo - S.C.D.U. Ematologia
🇮🇹Alessandria, Italy
A.O.U. Ospedali Riuniti delle Marche - Clinica di Ematologia
🇮🇹Ancona, Italy
I.R.C.C.S. Istituto Tumori Giovanni Paolo II - U.O.C. Ematologia
🇮🇹Bari, Italy
ASST Spedali Civili - S.C. Ematologia
🇮🇹Brescia, Italy
I.R.C.C.S. Istituto di Candiolo - FPO
🇮🇹Candiolo, Italy
I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncoematologia
🇮🇹Castelfranco Veneto, Italy
ARNAS Garibaldi - U.O.C. Ematologia
🇮🇹Catania, Italy
A.S.T. Macerata - U.O.S.D Ematologia
🇮🇹Civitanova Marche, Italy
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
🇮🇹Firenze, Italy
ASST Grande Ospedale Metropolitano Niguarda - S.C. Ematologia
🇮🇹Milano, Italy
Ospedale Maggiore Policlinico Fondazione IRCCS Ca' Granda - S.C. Ematologia
🇮🇹Milano, Italy
A.O.U. di Padova - U.O.C. Ematologia
🇮🇹Padova, Italy
I.R.C.C.S. Istituto Oncologico Veneto - U.O.C. Oncologia 1
🇮🇹Padova, Italy
A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia U
🇮🇹Torino, Italy
ULSS 2 Ospedale Ca' Foncello - U.O.C. Ematologia
🇮🇹Treviso, Italy
A.O. Cardinale "G. Panico" - U.O.C Ematologia e Trapianto Midollo Osseo
🇮🇹Tricase, Italy
A.S.U. Giuliano Isontina - S.C. Ematologia
🇮🇹Trieste, Italy
A.O.U.I. di Verona - Ematologia
🇮🇹Verona, Italy