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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 20
- 主要终点
- 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
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Primary lymphomas of the central nervous system, plasmablastic lymphoma, Burkitt's lymphoma, primary mediastinal B lymphoma
- •Have received palliative treatment
结局指标
主要结局
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
时间窗: 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
次要结局
- 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))
- 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))
- 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))
- 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))