Molecular Disease Profile of Haematological Malignancies. A Prospective Registry Study by the Rete Ematologica Lombarda (REL) Clinical Network
试验速览
- 阶段
- 不适用
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Cumulative incidence of gene mutations in principal clone and subclones in each hematological malignancy
研究概览
简要总结
In this prospective multicentric study, the University of Pavia together with the Fondazione IRCCS Policlinico San Matteo, Pavia and the IRCCS Fondazione Maugeri, Pavia, Italy will provide a systematic analysis of gene mutations in hematological malignancies by using NGS techniques. Patients with a conclusive diagnosis of haematological malignancies according to WHO criteria referred to the Rete Ematologica Lombarda clinical network (REL, www.rel-lombardia.net) will be enrolled. The investigators will analyse genomic DNA extracted from hematopoietic cells at different time points of patient disease. The study contemplates the use of molecular platforms (Next Generation Sequencing, NGS) aimed at the identification of recurrent mutations in myeloid and lymphoid neoplasms, respectively. Screening of gene mutations by NGS will be prospectively implemented in the context of REL clinical network. Patient samples will be analyzed at diagnosis and sequentially during the course of the disease at specific timepoints. The researchers will analyze the correlations between somatic mutations, specific clinical phenotypes (according to the WHO classification) and disease evolution. This will allow to: 1) identify new recurrent genetic mutations involved in the molecular pathogenesis of hematological malignancies; 2) define the role of mutated genes, distinguishing between genes which induce a clonal proliferation of hematopoietic stem cells, and genes which determine the clinical phenotype of the disease; 3) identify mutations which are responsible for disease evolution; 4) define the diagnostic/prognostic role of the identified mutations, and update the current disease classifications and prognostic scores by including molecular parameters. A systematic biobanking of biological material will be provided.
详细描述
- BACKGROUND
Molecular medicine is the branch of knowledge whose purpose is to elucidate the genetic basis of the diseases, to improve the diagnostic definition and prognostic assessment of patients and to contribute to the development of innovative treatments. Genomic information is increasingly being used in the treatment decision making process for individual patients. The clinical implementation of molecular medicine requires systematic approaches based on the integration of scientific, medical and technological expertises.
Hematological malignancies include leukemia, lymphoma, and multiple myeloma. The molecular basis of many hematological neoplasms are still unknown. At the present of researchers' knowledge, scientists know that hematological malignancies are mostly dynamic diseases that arise from a large series of primary and secondary biological and genetic events (i.e. driver and passenger mutations). The Identification of key molecular changes that drive tumour development and progression is essential for the development of new targeted and personalized therapies.
Hematological malignancies typically occur in elderly people and, as a result of population aging, represent a growing critical issue for health policies. Hematological malignancies are an ideal context for the implementation of molecular medicine. The paradigmatic example of this is chronic myeloid leukemia, in which the discovery of the molecular basis (the fusion gene BCR/ABL1) has been translated into major clinical advances in diagnosis, treatment and disease monitoring.
The World Health Organization (WHO) classification of myeloid and lymphoid neoplasm published in 2008 introduced many genetic changes in the diagnostic definition of blood cancers. Since 2008 plenty of genetic lesions have been identified in many hematological malignancies and the next WHO classification will include many of them.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Conclusive diagnosis of myeloid or lymphoid neoplasm according to 2008 WHO criteria
- •age ≥ 18 years. There is no upper age limit
- •signed written informed consent
- •Exclusion criteria:
- •severe neurological or psychiatric disorder interfering with ability to give an informed consent
- •no written informed consent
排除标准
- 未提供
结局指标
主要结局
Cumulative incidence of gene mutations in principal clone and subclones in each hematological malignancy
时间窗: 3 years
次要结局
- Genotype-phenotype correlations between clinical characteristics and mutational status(3 years)
- Overall survival and disease-free survival according to clinical and biological risk factors at diagnosis and during disease evolution(3 years)
研究者
Matteo Giovanni Della Porta
MD
University of Pavia