Identifying Cellular and Molecular Determinants of Efficacy and Resistance in Patients Undergoing CAR-T Therapy (CAR-Lille)

Identifying Cellular and Molecular Determinants of Efficacy and Resistance in Patients Undergoing CAR-T Therapy at the CHU, Lille: Biological Prospective Collection and Storage

In recent years we have witnessed a breakthrough in the treatment of leukemia and lymphoma using autologous CAR-T cells that can induce durable remission in patients. Multiple approved CAR-T therapy trials, including those at our centre, have consistently yielded objective tumor regression rates in about 40% of patients that have progressed after multiple previous chemo or targeted therapies. However, not all the patients respond to the therapy and rate of relapse is unfortunately common. Hence, the identification of biomarkers to track clinical activity of CAR-T and as predictive tools for patient selection is critical in our quest to develop personalized cellular therapies, where both degree and duration of response varies among different patients. For CAR-T therapy to truly live up to its promise, it is imperative to increase durable response rates. The success of CAR-T therapy not only depends in targeting antigens (e.x. CD19, BCMA) commonly expressed by malignant cells but also limited by poor persistence and trafficking of infused CAR-T cells in vivo. Hence highlighting the need to identify factors that exhibit optimal homing to the target sites and are able to persist long-term for continuous tumor surveillance. Furthermore, we lack comprehensive knowledge on how certain patients with leukemia and lymphoma achieve complete durable anti-cancer response upon CAR-T infusion whereas other either partially respond to the therapy and then relapse, or do not respond at all. Determining cellular and molecular factors that contribute to optimal homing of CAR-T cell to target sites as well as their long-term persistence will help us to design improved CAR-T based therapy against lymphoma other malignancies.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Hematologic Malignancy

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Ibrahim Yakoub-Agha, MD,PhD; Phone Number: +33 0320445962; Email: ibrahim.yakoubagha@chru-lille.fr

Study Locations

• France
  • Lille, France
    • Recruiting
    • CHU de Lille
    • Contact: ibrahim Yakoub-Agha; Phone Number: +33(0)3.20.44.55.51; Email: ibrahim.yakoubagha@chru-lille.fr
  • Lille, France, 59037
    • Terminated
    • Hop Claude Huriez Chu Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Samples from eligible patients who receives commercially available CAR-T therapy will be collected and stored at regular intervals

Description

Inclusion Criteria:

• Male or female aged ≥ 18 years and able to provide informed consent
• Any indication,
• Commercially available CART therapies,
• Any conditioning.

Exclusion Criteria:

• Freedom privacy
• Absence of medical coverage
• Patients receiving CART or CAR-based cellular therapies which are not commercially available.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment failure (progression and relapse) will be evaluated according to standard criteria	at 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performing Immunophenotyping of CAR T cells and lymphocyte subsets as well as functional tests for CAR T and the corresponding tumor samples.		at 10 years
Performing Immunophenotyping and single cell sequencing of circulating CAR T cell and those infiltrating the tumor		at 10 years
Measurement of serum cytokine levels		at 10 years
constitution of a biological collection (biobank)	Tests are done as needed (Immunophenotyping, DNA sequencing, cytokine measurement,..)	at 10 years

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Ibrahim Yakoub-Agha, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Estimated): February 18, 2028
• Study Completion (Estimated): February 18, 2028

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 2020_47; 2020-A01935-34 (Other Identifier: ID-RCB number,ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No