RT-CAR: Real-Time Monitoring of Circulating Tumor DNA and Study of Prognostic Factors in Patients Treated With CAR-T Cells

Sponsor

Centre Henri Becquerel (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05675982

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that it is possible to report in real time (less than 3 weeks) to the hematologist the results of the molecular minimal residual disease (MRD) based on blood circulating tumor DNA (ctDNA) assessment taken approximately 7 days after the reinjection of the CAR-T cells, in order to be able to anticipate a possible progression of the disease and to be able to propose salvage or earlier adjuvant therapy to improve patient prognosis.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Other: CAR-T cells monitoring	N/A

Detailed Description

The main objective is to demonstrate the feasibility of monitoring residual disease in real time by monitoring circulating tumor DNA in patients with relapsed or refractory diffuse large cell B-cell lymphoma treated with anti-CD19 CAR-T (axi-cel, tisa -cel or liso-cel).

The primary endpoint of the study is to assess the capacity of our research lab to transmit the result of the molecular characterization of the residual disease (MRD) sampled on Day+7 (+/- 3 days) of the injection of CAR-Ts (MRD evaluated by the quantity of ctDNA by NGS technique) of the patient with DLBCL R/R treated with CAR-T, to the recruiting investigator no later than Day+28 (+ /- 3 days). We will evaluate the proportion between the number of informative evaluable patients (patients with at least one detectable mutation in pre-treatment and having reached the PET-CT evaluation of Day+28) and the total number of informative patients (patients with at least one mutation detectable in pre-treatment). The target will be achieved and real-time MRD assessment will be considered feasible if the proportion is at least 80%.

Patients who do not have a detectable mutation in pre-treatment ("non-informative patients for follow-up of residual disease"), as well as patients who do not reach the ctDNA sample by Day+7, and/or do not not reaching the PET-CT by Day+28, will be considered as not evaluable for the primary endpoint, and will be the subject of a separate descriptive analysis and will be evaluable for the secondary objectives. We took this into account when evaluating the number of patients to include.

Day0 corresponds to the day of injection of the CAR-Ts, Day+7 corresponds to the 8th day post-injection of the CAR-Ts, and D+28 refers to the planned date of the PET-CT evaluation of Day+28 (this examination being the "gold standard" for the evaluation of the response to treatment with CAR-T).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Real-Time Monitoring of Circulating Tumor DNA and Study of Prognostic Factors in Patients Treated With Anti-CD19 CAR-T Cells for Relapsed or Refractory Diffuse Large B-cell Lymphoma

Anticipated Study Start Date :

Jan 2, 2023

Anticipated Primary Completion Date :

Jan 2, 2025

Anticipated Study Completion Date :

Jan 2, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Minimal residual disease assessment	Other: CAR-T cells monitoring monitoring of circulating DNA by blood sample

Arm

Intervention/Treatment

Experimental: Minimal residual disease assessment

Other: CAR-T cells monitoring

monitoring of circulating DNA by blood sample

Outcome Measures

Primary Outcome Measures

Time required to report minimal residual disease report [28 days]
To to assess the capacity of the research lab to transmit the result of the molecular characterization of the residual disease sampled on day 7 of the injection of CAR-Ts of the patient to the recruiting investigator no later than day 28.

Secondary Outcome Measures

Progression free survival [one year]
time between inclusion and progression
Overall survival [one year]
time between inclusion and death with all cause of mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 18 or over
Carriers of relapsed or refractory diffuse large cell B-cell lymphoma (LBDGC R/R), relapsed or refractory primary mediastinum B-cell lymphoma or follicular lymphoma transformed into LBDGC R/R
Patients with an indication for treatment with CAR-T anti CD19
PET-CT pre-injection of CAR-T performed
Signed informed consent
Patients affiliated or beneficiaries of a health insurance scheme

Exclusion Criteria:

Pregnant or breastfeeding women
Absence or insufficiency of tumor material (patient's most recent diagnostic biopsy) fixed in FFPE paraffin of insufficient quality/quantity for next-generation sequencing (NGS) analysis
Lack of patient consent
Patient treated with CAR-T as part of a therapeutic clinical trial
Patient whose weight is less than 30 kg
Protected adult or deprived of liberty (under guardianship or curatorship)
Patient unable to understand the study for any reason whatsoever or to comply with the constraints of the trial (language, psychological, geographic problem, etc.).