Neurocognitive Assessment in Adults Undergoing CD19 Targeted CAR-T Cell Therapy

NCT07463781 | Not Yet Recruiting

• 1 other identifier: FIL_NEURO_CAR-T
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 8

Brief Summary

This is an observational, multicenter, prospective cohort study including patients treated with CAR-T in Italian centers. Patients eligible for enrollment in the study will be consecutively included in Italian FIL centers. A longitudinal survey will be carried out by collecting patients' data before starting CAR-T (T0) and after 6 (T1), 12 (T2) and 24 (T3) months after CAR-T infusion.

Conditions

Diffuse Large B Cell Lymphoma (DLBCL); High Grade B Cell Lymphoma; Primary Mediastinal B-cell Lymphoma (PMBCL)

Outcome Measures

Primary Outcomes (19)

• Self-assessed neurocognitive performance

  Self-assessed neurocognitive performance will be evaluated through Functional Assessment of Cancer Therapy - Cognitive questionnaire (FACT-Cog Version 3). The FACT-Cog (Version 3) is a self-report questionnaire developed within the measurement system of FACIT.org (Functional Assessment of Chronic Illness Therapy) to assess perceived cognitive functioning in individuals with cancer. The instrument includes 37 items in total, although the most commonly reported total score is based on 33 scored items. Each item is rated on a 5-point Likert scale (0-4) (0 = not at all; 4 = very much / very often, depending on the item). Total score (33-item scoring): Minimum: 0, Maximum: 132. Score interpretation: higher scores indicate better perceived cognitive functioning, lower scores indicate greater perceived cognitive impairment.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Cognitive Status - Mini-Mental State Examination (MMSE)

  Cognitive status will be assessed using the Mini-Mental State Examination (MMSE). Unit of Measure: Total score (points) Range: 0 to 30 Interpretation: Higher scores indicate better cognitive performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Quality of Life (QoL)

  Quality of life will be evaluated through EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer-Quality of life Questionnaire-Core 30). The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) is a 30-item instrument used to assess health-related quality of life in people with cancer. All scales and single items are linearly transformed to a 0-100 scale (Minimum: 0 and Maximum: 100).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Psychological status

  Psychological status will be evaluated through HADS questionnaire (Hospital Anxiety and Depression Scale). The Hospital Anxiety and Depression Scale consists of two subscales: anxiety (HADS-A) and depression (HADS-D). Each subscale ranges from 0 to 21, with higher scores indicating worse psychological outcomes (greater anxiety or depression symptoms).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Resilience

  Resilience will be evaluated through RS-14 questionnaire (Resilience scale-14 questionnaire). The Resilience Scale-14 produces a total score ranging from 14 to 98, with higher scores indicating a better outcome (greater resilience).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Adverse events

  CRS (Cytokine Release Syndrome), ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome) and IEC-HS (Immune Effector Cell associated HLH-like Syndrome) will be graded according to ASBMT (American Society for Blood and Marrow Transplantation ) consensus grading, ICAHT (Immune effector cell-associated hematotoxicity) will be graded according to EHA/EBMT (European Hematology Association/European Society for Blood and Marrow Transplantation) consensus grading, other extrahematological toxicities will be graded according to the latest version of CTCAE criteria (Common Terminology Criteria for Adverse Events).

  The endpoint wil be evaluated at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Treatment characteristics: Previous Central Nervous System Prophylaxis

  History of Central Nervous System prophylaxis prior to CAR-T therapy, including intrathecal methotrexate and/or high-dose methotrexate, collected from medical records. Unit of Measure: Participants with previous CNS prophylaxis (%).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy)

• Overall Survival (OS)

  Overall Survival for all patients included in the study: defined as the time between the start of CAR-T until death from any cause.

  The endpoint will be evaluated from the beginning to the end of the study (at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Praxic Abilities - Rey-Osterrieth Complex Figure Test (Copy Condition)

  Praxic and visuoconstructive abilities will be assessed using the copy condition of the Rey-Osterrieth Complex Figure Test (ROCF). Unit of Measure: Total score (points) Range: 0 to 36 Interpretation: Higher scores indicate better praxic/visuoconstructive performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Verbal Memory - Rey Auditory Verbal Learning Test (Word List 3 Recall)

  Verbal memory will be assessed using Word List 3 recall from the Rey Auditory Verbal Learning Test (RAVLT). Unit of Measure: Number of words correctly recalled Range: 0 to 15 Interpretation: Higher scores indicate better verbal memory performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Visual Memory - Rey-Osterrieth Complex Figure Test (Delayed Recall)

  Visual memory will be assessed using the delayed recall condition of the Rey-Osterrieth Complex Figure Test (ROCF). Unit of Measure: Total score (points) Range: 0 to 36 Interpretation: Higher scores indicate better visual memory performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Language - Verbal Fluency Test

  Language function will be assessed using a Verbal Fluency Test (phonemic and/or semantic, as applicable). Unit of Measure: Number of correct words generated within the allotted time Range: No fixed maximum value Interpretation: Higher scores indicate better language performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance status: Attention and Processing Speed - Trail Making Test Part A

  Attention and processing speed will be assessed using Part A of the Trail Making Test (TMT-A). Unit of Measure: Completion time (seconds) Range: Continuous variable (no fixed maximum) Interpretation: Lower scores indicate better performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion).

• Neurocognitive performance evaluation: Executive Function - Trail Making Test Part B.

  Executive function will be assessed using Part B of the Trail Making Test (TMT-B). Unit of Measure: Completion time (seconds) Range: Continuous variable (no fixed maximum) Interpretation: Lower scores indicate better performance.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion)

• Neurocognitive performance evaluation: Attention and Processing Speed - Symbol Digit Modalities Test (Oral Version)

  Attention and processing speed will be assessed using the oral version of the Symbol Digit Modalities Test (SDMT). Unit of Measure: Number of correct substitutions Range: No fixed maximum value (administration time-dependent) Interpretation: Higher scores indicate better attention and processing speed.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion).

• Neurocognitive performance evaluation: Executive Function - Frontal Assessment Battery

  Executive function will be assessed using the Frontal Assessment Battery (FAB). Unit of Measure: Total score (points) Range: 0 to 18 Interpretation: Higher scores indicate better executive functioning.

  The endpoint wil be evaluated at screening (before starting CAR-T therapy), at 6, 12 and 24 months after CAR-T infusion (from the beginning of the study at least 24 months after CAR-T infusion).

• Treatment characteristics: Cumulative Anthracycline Dose

  Total cumulative dose of anthracycline chemotherapy received prior to CAR-T therapy, collected from medical records. Unit of Measure: Milligrams per square meter (mg/m²).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy).

• Treatment characteristics: Prior Radiotherapy Field

  Anatomical field of radiotherapy received prior to CAR-T therapy as recorded in medical records (e.g., mediastinal, cranial, total body irradiation, or other). Unit of Measure: Participants by radiotherapy field (%).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy).

• Treatment characteristics: Prior Radiotherapy Dose

  Total radiation dose delivered during previous radiotherapy treatments before CAR-T therapy, obtained from medical records. Unit of Measure: Gray (Gy).

  The endpoint wil be evaluated at screening (before starting CAR-T therapy).

Study Arms (1)

Patients with DLBCL/HGBL and PMBCL

Patients with previous diagnosis of Diffuse Large B Cell Lymphoma or High-Grade B Cell Lymphoma (DLBCL/HGBL), arising de novo or transformed from a previous indolent histotype (transformed Follicular Lymphoma or transformed Marginal Zone Lymphoma), Primary Mediastinal B Cell Lymphoma (PMBCL) scheduled to received CAR-T cell product according to Agenzia Italiana del Farmaco (AIFA) indications and technical data sheet of the drug

Other: Chimeric Antigen Receptor T-cells (CAR-T) therapy

Interventions

Chimeric Antigen Receptor T-cells (CAR-T) therapy OTHER

Patients will be treated with CAR-T cell product as per routine clinical practice.

Patients with DLBCL/HGBL and PMBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with previous diagnosis of Diffuse Large B Cell Lymphoma or High-Grade B Cell Lymphoma (DLBCL/HGBL), arising de novo or transformed from a previous indolent histotype (transformed Follicular Lymphoma or transformed Marginal Zone Lymphoma), Primary Mediastinal B Cell Lymphoma (PMBCL) scheduled to received CAR-T cell product according to Agenzia Italiana del Farmaco (AIFA) indications and technical data sheet of the drug

You may qualify if:

• Patients with previous diagnosis of Diffuse Large B Cell Lymphoma or High- Grade B Cell Lymphoma (DLBCL/HGBL), arising de novo or transformed from a previous indolent histotype (transformed Follicular Lymphoma or transformed Marginal Zone Lymphoma), Primary Mediastinal B Cell Lymphoma (PMBCL).
• Age over 18-years-old at the time of lymphoma diagnosis.

You may not qualify if:

• Patient with histological diagnosis of mantle cell lymphoma (MCL) or acute lymphoblastic leukemia (ALL)
• Patients with CNS disease localization.
• Patients that received brain/neuroaxis radiotherapy.
• Pre-existing severe psychiatric or neurologic comorbidities influencing neurocognitive assessment.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead
• Fondazione Lorenzo Farinelli Onlus: collaborator

Study Sites (8)

SCDU Ematologia - AOU SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Alessandria, Italy

Location

Clinica di Ematologia, AOU Ospedali Riuniti

Ancona, Italy

Location

USD-TMO Adulti - ASST Spedali Civili di Brescia

Brescia, Italy

Location

Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello

Palermo, Italy

Location

Ematologia - Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, Italy

Location

Ematologia - Università Cattolica S. Cuore

Roma, Italy

Location

SC Ematologia - Ospedale "S.G. Moscati"

Taranto, Italy

Location

SOC Clinica Ematologica - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)

Udine, Italy

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Immunotherapy, Adoptive; Therapeutics

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Immunologic Techniques; Investigative Techniques

Study Officials

• Luca Castagna

  A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uffici Studi FIL

CONTACT

+390131033153; startup@filinf.it

Uffici Studi FIL

CONTACT

+39 059 976 9911; gestionestudi@filinf.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: March 11, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-02

Locations

IT (8)