Clinical trial NCT05366569: Bio-CAR-T BS Study
Official title: Bio-CAR-T Study on Pre and Post-infusion CAR-T Cell Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Acute Lymphoblastic Leukemia (ALL)
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2022-05-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Calculation is based on the primary endpoints, i.e. the persistence of the CAR-T cells and the percentage of patients infused. As the Investigator have no formal statistical hypothesis to test, sample size justification is based on estimating the 95% confidence interval for the above percentage. Based on the UOC Hematology and Pediatric Oncohematology's experience and accrual potential, the Investigators are expecting about 180 patients newly diagnosed with DLBCL or PMBCL or ALL (potential candidate to CAR-T therapy) in a 3-year time window. About 25% of these patients are expected to be eligible to CAR T-cell treatment, corresponding to 45 patients. Thus, assuming a 25% percentage of patients infused, a sample size of 45 patients will produce a two-sided 95% confidence interval ranging from 12% to 38%, with a precision (half-width of 95% confidence interval) equal to 13%.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: 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))
measure: Change of disease burden after CAR-T Cells treatment
timeFrame: At day +30; +90; +180; 270 and + 360 post CAR-T infusion
Secondary outcomes:
measure: 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
timeFrame: 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)
measure: Evaluation of disease persistence and immune recovery and neurological biomarkers after CAR-T infusion
timeFrame: 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
measure: Evaluation of plasma level of biomarkers for ICANS neural damage and glial activation in patients who develop ICANS.
timeFrame: 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
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
Study officials:
References:
citation: 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 (Basel). 2022 Oct 27;14(21):5276. doi: 10.3390/cancers14215276.