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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
Sponsor:
Information provided by (Responsible Party):
Centre Henri Becquerel

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Primary Mediastinal Large B-cell Lymphoma Other: Circulating tumor DNA monitoring Not Applicable

Detailed Description:

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:

  1. Patients with "negative" plasma DNA at diagnosis (defined by the absence of somatic mutation detectable at diagnosis by ctDNA analysis)
  2. 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
  3. 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Monitoring of Circulating Tumor DNA Other: Circulating tumor DNA monitoring
Monitoring of circulating tumor DNA after 2 and 4 cycles of chemotherapy


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. overall survival [ Time Frame: 3 years ]
    Time between death and inclusion

  5. 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

  6. genic expression profile [ Time Frame: 3 years ]
    Next-Generation-sequencing on diagnostic biopsy

  7. Genomic sequencing of circulating tumor DNA [ Time Frame: 3 years ]
    Determination of molecular profile and evaluation of pronostic impact

  8. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.).
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: VINCENT CAMUS, MD +33232082497 vincent.camus@chb.unicancer.fr
Contact: RICHARD DORIANE, PhD +33232082985 doriane.richard@chb.unicancer.fr

Locations
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France
Centre Hospitalier Lyon Sud Not yet recruiting
Lyon, France
Contact: PIERRE SESQUES, MD    +33478864301    pierre.sesques@chu-lyon.fr   
Centre Henri Becquerel Recruiting
Rouen, France
Contact: VINCENT CAMUS, MD    +33232082947    vincent.camus@chb.unicancer.fr   
Sponsors and Collaborators
Centre Henri Becquerel
Investigators
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Principal Investigator: VINCENT CAMUS, MD Centre Henri Becquerel
Principal Investigator: PIERRE SESQUES, MD Centre Hospitalier Lyon Sud
More Information
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Responsible Party: Centre Henri Becquerel
ClinicalTrials.gov Identifier: NCT04824950    
Other Study ID Numbers: CHB20.03
First Posted: April 1, 2021    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Henri Becquerel:
Primary Mediastinal Large B-cell Lymphoma
Circulating tumor DNA
Next Generation sequencing
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin