Immunotherapy with Differentiated T Cells, Adults, Autologous, From Peripheral Blood, Selected by CD62L Expression, Expanded and Transduced (Genetically Modified) Through a Lentiviral Vector to Express a Chimeric Receptor with ANTI-CD19 Specificity Associated with Co-Stimulatory Sequences 4-1-BB and CD3 in Patients with B-Cell Non-Hodgkin Lymphoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

24 Jan 2025 → ongoing

Decision date (initial)

2025-01-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519790-19-00

EudraCT number

2020-003133-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

Evaluate the safety, toxicity, and efficacy of the administration of autologous memory T cells, mature, expanded ex vivo and genetically modified with a chimeric antigen receptor (CAR) targeting the CD19 antigen

Secondary objectives 5

1. Analyze the persistence of CAR19 T cells
2. Analyze the response rate at 3 months post-procedure.
3. Analyze the impact of the procedure on progression-free survival at 2 years.
4. Analyze overall survival (OS) at 2 years.
5. Analizar el implante y persistencia de las células T-CAR19.

Conditions and MedDRA coding

Relapsed/refractory large B-cell non-Hodgkin lymphoma, mantle cell lymphoma, and follicular lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Age > 18 years
2. General condition according to ECOG scale: 0-2.
3. FEV1 > 40%; DLCO and FVC > 40% of the predicted normal values.
4. Absence of significant ventricular dysfunction: left ventricular ejection fraction > 40%.
5. Total bilirubin and transaminases < 4 times the upper normal limit, unless attributable to lymphoma.
6. Creatinine < 2 times the upper normal limit and clearance > 40 mL/min.
7. Negative serology for HIV, HBV, and HCV. For patients with positive serology for HBV or HCV, a viral load of 0 must be confirmed via quantitative PCR.
8. Absence of uncontrolled active bacterial, viral, or fungal infection.
9. All patients must sign an informed consent form prior to the initiation of any procedure.
10. All patients must have measurable disease (detected by PET-CT or CT) at the time of inclusion.
11. Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Histological diagnosis (WHO) of LDCGB or grade 3B follicular lymphoma, and Relapsed or refractory to 2 lines of treatment (including doxorubicin and anti-CD20 monoclonal antibody) or relapse after autologous hematopoietic stem cell transplantation from peripheral blood.
12. Patients with Mantle Cell Lymphoma (MCL): Histological diagnosis (WHO) of MCL, including classical and blastoid variants, and Relapsed or refractory after two lines of treatment, which must include an anti-CD20 monoclonal antibody and a BTK inhibitor, or relapse after an autologous hematopoietic stem cell transplantation in patients who previously received a BTK inhibitor.
13. Patients with Follicular Lymphoma (FL): Histological diagnosis (WHO) of FL grade 1-3a, and Relapsed or refractory to two lines of treatment (including anti-CD20 monoclonal antibody) or meet the criteria for early relapse (POD24) within the first 24 months after the start of initial treatment: relapse/refractoriness after one treatment (including anti-CD20 monoclonal antibody) or relapse after autologous hematopoietic stem cell transplantation.

Exclusion criteria 14

1. General condition determined by ECOG scale: 3-4.
2. Active infection with HBV or HCV.
3. HIV infection.
4. Uncontrolled active bacterial, fungal, or viral infection.
5. Active CNS infiltration by lymphoma. Previous lymphoma infiltration is not exclusionary if there is evidence of absence of disease in the CNS prior to treatment.
6. Abnormal renal and hepatic function, with creatinine and/or bilirubin levels more than 2 and 4 times higher than the normal limit, respectively, except when the abnormalities are attributable to lymphoma (only in cases of hepatic alteration).
7. Patients with a left ventricular ejection fraction (LVEF) less than 40%, symptomatic heart failure, or both.
8. Presence of cirrhosis.
9. Patients with concomitant severe neurological or psychiatric disease.
10. Presence of active autoimmune or rheumatologic disease requiring systemic treatment with any immunosuppressor.
11. Lung disease of any type that results in a DLCO < 40%.
12. Major surgery within 6 weeks prior to inclusion.
13. Any concomitant anticancer treatment.
14. Pregnant or breastfeeding patients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety associated with the infusion of HSP-CAR19M cells. In the expansion phase: evaluation of the safety and efficacy of HSP-CAR19M cell administration.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Address

Calle Sant Quinti 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Contact name

Alejandra Espinosa

Public contact point

Organisation

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

Contact name

Alejandra Espinosa

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications