Aggressive B-cell Lymphomas
Conditions
Keywords
Circulating Tumor DNA, Measurable Residual Disease, Large B-Cell Lymphoma, PhasED-Seq, PET-Scan in Lymphoma
Brief summary
RT4 (REAL TIME TAILORED THERAPY) study was designed as a national, multicenter proof of concept aiming to demonstrate the technical and operational capacity of the French Connect network and the Positron Emission Tomography (PET) review network to ensure, within a coordinated framework, real time MINIMAL RESIDUAL DISEASE (MRD) monitoring through ctDNA analysis and centralized review of PET imaging.
Detailed description
Monitoring measurable residual disease (MRD) through the analysis of circulating tumor DNA (ctDNA) in plasma is rapidly emerging as one of the major recent advances in the management of lymphomas. Over the past years, several studies have shown that ctDNA enables a dynamic and highly sensitive assessment of treatment response, surpassing the limitations of conventional approaches based on imaging only. Importantly, these advances do not replace or diminish the role of PET imaging. On the contrary, metabolic imaging and molecular monitoring are increasingly seen as complementary tools. When used together, PET imaging and ctDNA kinetic analysis may dynamically refine risk stratification and enable truly individualized adaptive treatment strategies. However, this synergy between MRD and PET can only influence clinical practice or trial design if results are available throughout patient management within a timeframe compatible with therapeutic decision making.
Interventions
OTHERblood test
Three blood tests will be performed (one before treatment, one at mid treatment, and one at the end of treatment) for ctDNA analysis.
Sponsors
The Lymphoma Academic Research Organisation
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be included in the study: 1. Participant who understands and voluntarily signs an informed consent form prior to any study-specific assessment or procedure. 2. Age 18 or older at the time of signing the Informed Consent Form (ICF) 3. Histologically confirmed diagnosis, according to the WHO 2022 classification, of any of the following lymphomas: Aggressive B-cell lymphoma, including: * Diffuse large B-cell lymphoma, unspecified (DLBCL not specified) * High-grade B-cell lymphoma (LBHG), including: 1. With rearrangements of the MYC and BCL2 and/or BCL6 genes (double/triple hit) 2. Unspecified (i.e., no double/triple rearrangement) * Primary B-cell lymphoma of the mediastinum (PMBL) * Transformed indolent B-cell lymphoma, including: 1. Transformed follicular lymphoma (LFt) 2. Transformed marginal zone lymphoma (t-MZL) 3. Transformed, unspecified nodal or splenic B-cell lymphomas (NOS) 4. Presence of a measurable disease on pre-therapeutic PET imaging, defined as at least one two-dimensional measurable nodal lesion, defined as \> 1.5 cm in its largest dimension (and FDG-greedy lesion), or at least one two-dimensional measurable extranodal lesion, defined as \> 1.0 cm in its largest dimension (and FDG-hungry lesion). 5. Requiring standard first-line systemic treatment with curative intent 6. Person covered by a social security scheme 7. Person able to understand and speak French.
Exclusion criteria
Participants who meet any of the criteria below will not be eligible for inclusion / should be excluded from the study: 1. Systemic anticancer treatment of current lymphoma prior to inclusion in the study. All participants must be previously untreated for current lymphoma. Note: Short-term corticosteroid therapy (e.g., for symptom control or as part of diagnostic workup) is allowed prior to inclusion and is not an exclusion criterion. 2. Lymphomas associated with an immuno-privileged site (e.g., primary central nervous system lymphoma, primary testicular lymphoma, primary vitreoretinal lymphoma). 3. Absence of mandatory blood sampling for the analysis of circulating tumor DNA (ctDNA) during screening (pre-therapeutic sampling). 4. Absence of 18F-FDG PET examination performed within 2 months ≤ the date of signing the consent (mandatory pre-therapeutic PET imaging). 5. Pregnant, intending to be pregnant, or breastfeeding woman of childbearing potential 6. Any significant medical condition, laboratory abnormality, or psychiatric illness that may interfere with participation in this clinical study (in the opinion of the investigator) 7. Person deprived of liberty by judicial or administrative decision 8. Person hospitalized without their consent 9. Adult under legal protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary endpoint is the proportion of participants for whom MRD results are delivered within these timelines at the predefined interim treatment response assessment. | at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) | The primary objective of the study is to assess the feasibility of providing investigators with MRD results for participants with previously untreated aggressive B cell lymphomas at the time of the predefined interim response assessment, within strict timelines: * no more than 14 calendar days from blood collection for ctDNA results, and * no more than 7 calendar days after the imaging examination for the centralized PET review results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | at 1 year | Event Free Survival (EFS) by histology subtype |
| Progression/relapse | at 1 year | Duration of response (DoR) as defined by Lugano 2014 criteria |
| Evaluate the prognostic value of ctDNA/radiomics PET at mid-treatment and end-of-treatment | at 1 year | PFS according to ctDNA MRD status at the interim assessment and at the end of treatment assessment (positive vs negative), according to the interim PET response (response per Lugano 2014 and other radiomic parameters), and according to their combination (ctDNA + PET). |
| To document and classify the reasons for unsuccessful PET acquisition, analysis or reporting | at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) | Number of participants with delayed results, and reasons associated. |
| Number of participants with concordant results (positive PET and ctDNA or negative PET and ctDNA) and number of participants with discordant results (positive PET and negative ctDNA or negative PET and positive ctDNA). | Each timepoint (pre-treatment, interim timepoint, end of treatment) | Concordance rate between metabolic PET response and ctDNA result |
| To document and classify the reasons for unsuccessful ctDNA sampling, processing or result reporting. | at interim timepoint, after Cycle 4 (each cycle is 14 or 21 days) | Number of participants with delayed results, and reasons associated. |
| To assess the proportion of informative cfDNA samples for phased variant monitoring | Baseline | Proportion of samples with at least twenty phased variants detectable at baseline |
| Describe the timelines for the delivery of the results of the centralized PET review. | Two timepoints (Baseline, end of treatment) | Proportions of participants for whom results are delivered within the predefined time frame in the protocol (time between the date of image acquisition or collection and the date of transmission to the investigator ≤ target time), at baseline (before interim evaluation) and at the end of treatment (≤ 5 weeks) with a 95% confidence interval. The observed delays (in calendar days) will also be described by their distribution (median, interquartile range, minimum-maximum) |
| Describe the timelines for the delivery of the results of ctDNA results. | Two timepoints (Baseline, end of treatment) | Proportions of participants for whom results are delivered within the predefined time frame in the protocol (time between the date of blood collection and the date of transmission to the investigator ≤ target time), at baseline (before interim evaluation) and at the end of treatment (≤ 5 weeks), estimated globally and by RT4 platform with a 95% confidence interval. The observed delays (in calendar days) will also be described by their distribution (median, interquartile range, minimum-maximum), overall and by platform |
Countries
France
Contacts
CONTACTProject Management Project Management
PRINCIPAL_INVESTIGATORVincent CAMUS, Dr
CENTRE HENRI BECQUEREL - Service Hématologie
PRINCIPAL_INVESTIGATORCédric ROSSI, Pr
CHU DIJON BOURGOGNE - Service Hématologie Clinique
Outcome results
None listed