Circulating Tumor DNA in Primary Mediastinal Large B-cell Lymphoma (PMBL)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 87
- 试验地点
- 2
- 主要终点
- Correlation between circulating tumoral DNA detection and complete molecular response
研究概览
简要总结
The purpose of this study is to compare the predictive value in terms of specificity of circulating tumor DNA (ctDNA) and positron emission computed tomography (PET-CT) after 2 cycles of chemotherapy (C2), on the probability of obtaining a metabolic complete response after 4 cycles of induction chemotherapy (C4) in patients with primary mediastinal large B cell lymphoma (PMBL) receiving standard R-CHOP14 or R-ACVBP.
详细描述
The majority of studies with PMBL patients pinpoint the importance of being able to identify primary chemo refractory patients at an early stage, in order to be able to improve their prognosis. Indeed, a biomarker such as circulating tumor DNA (ctDNA) monitoring would be of great help to better assess the therapeutic response and offer an individualized care given the frequent positive residual uptake of the mediastinum at end of treatment. Indeed, ctDNA can be detected with Next-Generation Sequencing (NGS).
The hypothesis of this study is that it would be helpful to prospectively compare the predictive value of ctDNA versus PET on the capacity to detect primary refractory patients after 2 or 4 cycles of first line chemotherapy.
To date, there are no prospective studies reporting the evolution of the tumor clone under treatment or after obtaining complete remission in PMBL. The establishment of this prospective, multicenter, ambitious and original pilot project will make it possible to structure the analysis of tumor DNA circulating within these centers caring for patients with lymphomas within LYSA group.
The notion of minimal residual disease (MRD) has shown its interest in follicular lymphomas and mantle cell lymphomas. The level of sensitivity of NGS-type approaches on the one hand and the informativeness of the recurrent mutations recently described on the other hand constitute two elements for reconsidering the problem of MRD in PMBLs. Molecular MRD by analysis of circulating tumor DNA could constitute a new marker for monitoring response to treatment in addition to PET-CT and be useful as a tool for non-invasive tumor sequencing at diagnosis and at relapse, in order to to determine the eligibility for possible targeted therapies (based on the inactivation of mutated genes) or immunotherapies.
This study will evaluate the prognostic value of obtaining a quantified complete molecular response (RMC) by analysis of free circulating DNA (ctDNA) after 2 and 4 cycles of first-line chemotherapy (C2 and C4) for the treatment of PMBL, and that of positron emission computed tomography (PET) performed at the same time, on overall survival and progression-free survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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
- •Patient over 18 years of age,
- •Suffering from a diffuse primary B lymphoma of the mediastinum, newly diagnosed locally on a biopsy with anatomopathological analysis according to the recommendations of the WHO 2016 classification of hematological malignancies,
- •All stages (I-IV)
- •All IPI scores (0-5)
- •With mediastinal involvement,
- •Untreated (apart from emergency corticosteroid therapy less than 2mg/kg/day for 7 days),
- •Treatment with R-CHOP-14 or R-ACVBP with PET-CT guided strategy (delta SUVmax) to be initiated,
- •Tumor fixation above liver background on pre-treatment FDG PET/CT/CT (Deauville score ≥4),
- •Having signed the informed consent prior to any study procedure
- •Affiliated or beneficiary of a social protection plan.
排除标准
- •Patient who has already started chemotherapy treatment,
- •Contraindication to FDG PET-CT,
- •No mediastinal involvement,
- •Positive HIV serology,
- •Positive hepatitis B or C serology with positive viral load,
- •Protected adult (under guardianship or curatorship),
- •Pregnant or breastfeeding women,
- •Patient unable to understand the study for any reason or to comply with the constraints of the trial (language, psychological, geographical problems, etc.).
结局指标
主要结局
Correlation between circulating tumoral DNA detection and complete molecular response
时间窗: 4 months
specificity of ctDNA at Cycle 2 of chemotherapy on the prediction of achieving a complete metabolic response (determined by PET-CT scan) at cycle 4 of chemotherapy
次要结局
- genic expression profile(3 years)
- Genomic sequencing of circulating tumor DNA(3 years)
- Evaluation of complete metabolic response(at the end of first line treatment)
- Evaluation of response(At the end of treatment)
- Correlation between Next-Generation-Sequencing on tumor and molecular profile obtained on circulating tumor DNA(3 years)
- overall survival(3 years)
- Event free survival(3 years)