Bio-CAR-T BS Study

Официальное название

Bio-CAR-T Study on Pre and Post-infusion CAR-T Cell Therapy

Обзор

The aim of this Study is the evaluation of post-infusion CAR-T (Chimeric Antigen Receptor T Cell) expansion and persistence in patients with DLBCL, PMBCL and ALL undergoing CAR-T therapy; and the feasibility and efficacy of the treatment in the real life practice.

Подробное описание

This Study is characterized by several biological sub-studies, reported as below:

* Post-infusion CAR-T expansion and persistence analysis by both Flow Cytometry and digital PCR (dPCR): the aim of this point are the evaluation and enumeration of CAR T cells (CD4+ and/or CD8+) during patients follow-up and set up of specific panels for longitudinal evaluation and monitoring of CAR-T subsets. * Circulating Extracellular Vesicles quantification and analysis on peripheral blood and CNS (Central Nervous System) liquor: the aim are the identification of alterations in small EVs (Extracellular vesicles) ( number and cargos composition (proteins or miRNA) after CAR-T cell infusion and identification of small EVs markers which may distinguish patients "good responders" from patients "not responders" and/or which may predict particular post-infusion complications. * Evaluation of neurological markers for ICANS (Immune effector cell-associated neurotoxicity syndrome): the purpose of this substudy are the assessment of previously identified plasma and CSF (Cerebrospinal fluid)biomarkers for inflammation, neuronal damage and glial activation in patients who develop ICANS and the characterize temporal neuronal and glial involvement by assessing plasma and CSF inflammatory, neuronal and glial biomarkers in ICANS and their role on outcome.

Первичные конечные точки

• Evaluation of change post-infusion CAR-T cell expansion and persistence in patients with DLBCL, PMBCL and ALL undergoing CAR-T therapy evaluated by flow-cytometry and measures by number of cells/mL [Срок оценки: At day +1; +3; +7; +10; +14; +21; +30; +60; +90; +120; +150; +180; +210; +240; +270; +300; +330; +360 post CAR-T cell infusion or at any time for relapse/CRS-ICANS onset (assessed up to 2 years))]
• Change of disease burden after CAR-T Cells treatment [Срок оценки: At day +30; +90; +180; 270 and + 360 post CAR-T infusion]

Вторичные конечные точки (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v 4.0 and ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells [Срок оценки: At day +1; +3; +7; +10; +14; +21; +30; +60; +90; +120; +150; +180; +210; +240; +270; +300; +330; +360 post CAR-T cell infusion or at any time for relapse/CRS-ICANS onset (assessed up to 2 years)]
• Evaluation of disease persistence and immune recovery and neurological biomarkers after CAR-T infusion [Срок оценки: Before starting the treatment and at day +1; +3; +7; and +30 after infusion of CAR-T cell and in case of development of neurological symptoms]
• Evaluation of plasma level of biomarkers for ICANS neural damage and glial activation in patients who develop ICANS. [Срок оценки: Before starting the treatment and at day +1; +3; +7; and +30 after infusion of CAR-T cell and in case of development of neurological symptoms]

Критерии участия

Критерии включения

• Patients with B-cell-ALL (≤ 25 years) or patients with DLBCL (18-70 years) or patients with PMBCL (18-70 years) who were relapsed/refractory after two lines of treatments;
• Adequate performance status (0 or 1);
• Adequate organ function;
• No active or uncontrolled infections;
• No thrombo-embolisms within the last 6 months;
• Absence of clinically relevant co-morbidities (e.g., select cardiovascular, neurologic, or immune disorders with organ dysfunction or requiring immunosuppressive treatment in the last 24 months);
• Life expectancy of at least 3 months.

Критерии исключения

• Patients with B-cell-ALL > 25 years
• Patients with DLBCL <18 or >70 years
• Patients with PMBCL <18 or >70 years
• Performance status > 1;
• Active or uncontrolled infections;
• Thrombo-embolisms within the last 6 months;
• Presence of clinically relevant co-morbidities (e.g., select cardiovascular, neurologic, or immune disorders with organ dysfunction or requiring immunosuppressive treatment in the last 24 months);
• Life expectancy < 3 months.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

Италия · 1 центр

• ASST Spedali Civili di Brescia — Brescia

Публикации

• Farina M, Chiarini M, Almici C, Accorsi Buttini E, Zuccala F, Piva S, Volonghi I, Poli L, Bernardi S, Colnaghi F, Re F, Leoni A, Polverelli N, Turra A, Morello E, Galvagni A, Moratto D, Brugnoni D, Cattaneo C, Ferrari E, Bianchetti A, Malagola M, Re A, Russo D. Timely Leukapheresis May Interfere with the "Fitness" of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients. Cancers (B PMID 36358694

Идентификаторы

NCT: NCT05366569 · BIO-CAR-T BS 2022

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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