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

Официальное название

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

Обзор

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.

Первичные конечные точки

• Treatment failure (progression and relapse) will be evaluated according to standard criteria [Срок оценки: at 10 years]

Вторичные конечные точки (4)

• Performing Immunophenotyping of CAR T cells and lymphocyte subsets as well as functional tests for CAR T and the corresponding tumor samples. [Срок оценки: at 10 years]
• Performing Immunophenotyping and single cell sequencing of circulating CAR T cell and those infiltrating the tumor [Срок оценки: at 10 years]
• Measurement of serum cytokine levels [Срок оценки: at 10 years]
• constitution of a biological collection (biobank) [Срок оценки: at 10 years]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 2 центра

• Hop Claude Huriez Chu Lille — Lille
• chu de Lille — Lille

Идентификаторы

NCT: NCT07609485 · 2020_47 · 2020-A01935-34

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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