Circulating Tumor DNA in Primary Mediastinal Large B-cell Lymphoma (PMBL) (CAMIL)
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|ClinicalTrials.gov Identifier: NCT04824950|
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : April 1, 2021
|Condition or disease||Intervention/treatment||Phase|
|Primary Mediastinal Large B-cell Lymphoma||Other: Circulating tumor DNA monitoring||Not Applicable|
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.
The investigators will describe 3 different populations of patients included in the study:
- Patients with "negative" plasma DNA at diagnosis (defined by the absence of somatic mutation detectable at diagnosis by ctDNA analysis)
- Patients with "positive" plasma DNA at diagnosis (defined by the presence of at least one somatic mutation detectable at diagnosis by ctDNA analysis) and whose plasma DNA becomes "negative" after 2 cycles of chemotherapy
- Patients with "positive" plasma DNA and whose plasma DNA remains "positive" after 2 cycles of chemotherapy For these 3 patient profiles, we will perform comparisons, search for correlations with different variables and perform univariate and multivariate statistical analyzes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||87 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Circulating Tumor DNA in Primary Mediastinal Large B-cell Lymphoma (PMBL)|
|Estimated Study Start Date :||March 22, 2021|
|Estimated Primary Completion Date :||March 1, 2028|
|Estimated Study Completion Date :||March 1, 2028|
|Monitoring of Circulating Tumor DNA||
Other: Circulating tumor DNA monitoring
Monitoring of circulating tumor DNA after 2 and 4 cycles of chemotherapy
- Correlation between circulating tumoral DNA detection and complete molecular response [ Time Frame: 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
- Evaluation of complete metabolic response [ Time Frame: at the end of first line treatment ]Proportion of patient in complete metabolic response at the end of first line treatment
- Evaluation of response [ Time Frame: At the end of 4 cycles of chemotherapy ]Percentage of patients in complete metabolic response, partial metabolic response, stable disease or pregression after 4 cycles of chemotherapy
- Evaluation of response [ Time Frame: At the end of treatment ]Percentage of patients in complete metabolic response, partial metabolic response, stable disease or pregression at the end of treatment
- overall survival [ Time Frame: 3 years ]Time between death and inclusion
- Event free survival [ Time Frame: 3 years ]Lenght of time after the end of tratment and events like progression, lake of response, relapse of death whatever the cause
- genic expression profile [ Time Frame: 3 years ]Next-Generation-sequencing on diagnostic biopsy
- Genomic sequencing of circulating tumor DNA [ Time Frame: 3 years ]Determination of molecular profile and evaluation of pronostic impact
- Correlation between Next-Generation-Sequencing on tumor and molecular profile obtained on circulating tumor DNA [ Time Frame: 3 years ]Comparison between the result of Next generation Sequencing and the molocular profile obtained on circulation tumor DNA of each patient
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04824950
|Contact: VINCENT CAMUS, MDfirstname.lastname@example.org|
|Contact: RICHARD DORIANE, PhDemail@example.com|
|Principal Investigator:||VINCENT CAMUS, MD||Centre Henri Becquerel|
|Principal Investigator:||PIERRE SESQUES, MD||Centre Hospitalier Lyon Sud|