Diffuse Large B Cell Lymphoma (DLBCL)NCT05366569
Bio-CAR-T BS Study
An observational study of Diffuse Large B Cell Lymphoma (DLBCL) and Primary Mediastinal Large B-cell Lymphoma (PMBCL), run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diffuse Large B Cell Lymphoma (DLBCL), Primary Mediastinal Large B-cell Lymphoma (PMBCL), Acute Lymphoblastic Leukemia (ALL)
- How many people
- 45 participants
- Where
- 1 siteItaly
- Study dates
- 26 Apr 2022to 31 Dec 2026
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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%.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
ASST Spedali Civili di Brescia
Brescia, 25123
Domenico Russo, MD, 00390303996811, domenico.russo@unibs.it
Mirko Farina, MD, 00390303996811, m.farina004@unibs.it
About this study
Official title: Bio-CAR-T Study on Pre and Post-infusion CAR-T Cell Therapy
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.
Read the 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.
- Conditions
- Diffuse Large B Cell Lymphoma (DLBCL), Primary Mediastinal Large B-cell Lymphoma (PMBCL), Acute Lymphoblastic Leukemia (ALL)
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Disease response will be evaluated according to Lugano criteria
Measured: At day +30; +90; +180; 270 and + 360 post CAR-T infusion
Secondary outcomes (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
CTCAE v 4.0 and ASTCT (American Society for Transplantation and Cellular Therapy) Consensus Grading for Cytokine Release Syndrome (CRS) and Neurologic Toxicity Associated with Immune Effector Cells
Measured: 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
In addiction to cytokine panel (IL-1, IL-2, IL-5, IL-6, IL-7, IL-10, IL-12, IL-15, IL-17A, GM-CSF, TNFα, IFNγ, IL-22, IL-23) as per normal clinical practice the investigators will process interleukin: IL 8, IL 1β and CP-1.
Cytokine profiles will be analyzed from blood and CSF samples using Luminex platform and all the measure element will expressed in pg/mL.
Measured: 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.
Evaluation of previously identify plasma and CSF biomarkers for inflammation,neural damage and glial activation in patients who develop ICANS.
NfL and GFAP markers of neuronal injury and astroglia will be analyzed by SIMOAQuanterix, while sTREM2 (microglia activation) by Luminex, together with cytokines analysis.
The unit of measurement will be pg/mL.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2022
- Study start26 Apr 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B Cell Lymphoma (DLBCL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof Domenico Russo, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05366569
- Sponsor's protocol ID
- BIO-CAR-T BS 2022
- Status last verified
- Oct 2025
- First submitted
- 22 Apr 2022
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36358694