Cancer, Hematologic Malignancy
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
University Hospital, Lille
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment failure (progression and relapse) will be evaluated according to standard criteria | at 10 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | at 10 years | Tests are done as needed (Immunophenotyping, DNA sequencing, cytokine measurement,..) |
Countries
France
Contacts
CONTACTIbrahim Yakoub-Agha, MD,PhD
PRINCIPAL_INVESTIGATORIbrahim Yakoub-Agha, MD,PhD
University Hospital, Lille
Outcome results
None listed