Study of the Clearance of Minimal Residual Disease Measured at the End of First-line Treatment in Patients Treated for B-cell Lymphoma or Hodgkin Lymphoma
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Centre Henri Becquerel
- Enrollment
- 108
- Locations
- 4
- Primary Endpoint
- Evaluation of the diagnostic performance of minimal residual disease (MRD) at the end of treatment in terms of sensitivity, specificity, positive predictive value, and negative predictive value for predicting 1-year progression-free survival (PFS).
Study Overview
Brief Summary
This study aims to assess the feasibility of predicting patient outcomes at 1 year and 2 years after the end of first-line treatment using "liquid biopsy" (monitoring of circulating tumor DNA, ctDNA), compared to the currently recommended examination, which is Positon Emission Tomography (PET-CT) imaging at the end of first-line treatment (assessment of therapeutic response using the Deauville score according to the Lugano 2014 criteria). The study will focus on demonstrating the ability of ctDNA clearance to predict 1-year and 2-year outcomes (lymphoma progression or death) in patients treated with first-line therapy for B-cell lymphoma or Hodgkin lymphoma. This could contribute to establishing minimal residual disease clearance as a key endpoint for evaluating the efficacy of therapeutic strategies in future clinical trials and guiding patient management (e.g., de-escalation or intensification strategies, redirection toward immunotherapy, and theranostic approaches).
Detailed Description
Over the past decade, molecular biology methods known as "liquid biopsy" tools have emerged to identify tumor genotypes without a traditional biopsy, using blood samples and sequencing of circulating tumor DNA (ctDNA). Evidence supporting ctDNA's ability to perform comprehensive tumor genotyping, serving as an accurate reflection of the tumor genotype, has been well-documented in the literature. Two key aspects of the clinical relevance and routine applicability of ctDNA are currently under investigation:
The potential to measure and monitor the clearance of minimal residual disease (MRD) during and after treatment, which heavily depends on the detection limit and sensitivity of the analytical method.
The ability to deliver ctDNA analysis results to clinicians in real time, within timelines compatible with patient decision-making.
At Rouen, the investigators now use a method based on Unique Molecular Identifiers (UMIs), a type of molecular barcode that provides increased precision during sequencing. These molecular barcodes are short sequences used to uniquely label each DNA molecule in a sample library, minimizing false positives caused by random sequencing errors. By incorporating individual barcodes into each original DNA fragment, true variants in the original sample can be distinguished from errors introduced during library preparation, target enrichment, or sequencing.
The investigators have developed a new Next Generation sequencing (NGS) panel dedicated to ctDNA analysis using UMIs, encompassing 101 genes and 133 Kb of sequencing regions with phased variants on an Illumina® pipeline.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient aged 18 years or older
- •Diagnosed with large B-cell lymphoma (including T-cell/histiocyte-rich B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma), follicular B-cell lymphoma (all grades), mantle cell lymphoma (all variants), marginal zone B-cell lymphoma, or Hodgkin lymphoma (classical Hodgkin lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma)
- •Indication for first-line systemic treatment with chemotherapy or chemoimmunotherapy
- •Has signed the study-specific informed consent form
- •Pre-treatment PET-CT scan performed
- •Patient is affiliated with or a beneficiary of a health insurance plan
Exclusion Criteria
- •Pregnant or breastfeeding woman
- •Patient who has already started first-line chemotherapy or chemoimmunotherapy for lymphoma treatment (prephase corticosteroid therapy is allowed)
- •Patient enrolled in a clinical trial evaluating an early-phase therapeutic agent (Phase I-II)
- •Patient weighing less than 30 kg
- •Adult under legal protection measures
- •Patient unable to understand the study for any reason or unable to comply with the trial requirements (e.g., language barrier, psychological, or geographic issues).
Arms & Interventions
CELERITY Arm
CT DNA Collection at baseline, mid-treatment and at the end of treatment
Intervention: Blood assessment (Other)
Outcomes
Primary Outcomes
Evaluation of the diagnostic performance of minimal residual disease (MRD) at the end of treatment in terms of sensitivity, specificity, positive predictive value, and negative predictive value for predicting 1-year progression-free survival (PFS).
Time Frame: 1 year
Comparison with the diagnostic performance of PET-CT imaging at the end of first-line treatment for predicting 1-year PFS
Secondary Outcomes
- Response rates(6 months)
- Overall survival(one year)