Inmmunotherapy with peripheral blood, autologous, a dult T cells, expanded and transduced (gene modified) with a lentiviral vector expressing an anti-CD30-chimeric antigen receptor with 4-1-BB and CD3z costimulatory sequences in patients with Classical Hodgkin lymphoma and non-Hodgkin CD30+ T cell 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] - Neoplasms [C04]

Trial duration

17 Dec 2024 → ongoing

Decision date (initial)

2024-12-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515624-36-00

EudraCT number

2019-001263-70

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety and toxicity of HSP-CAR30 cell administration.

Conditions and MedDRA coding

Refractary or relapse non-Hodgkin T CD30+ lymphoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. All patients must sign informed consent before the start of any procedure.
2. All patients must have measurable disease (detected by PET-CT) at the time of inclusion.
3. Patients with classic Hodgkin's disease: 1. Age 18-80 years or older
4. Patients with classic Hodgkin's disease: 2. Patients in relapse after an autologous transplant of hemopoietic progenitors and who have previously received brentuximab vedotin and anti-PDL1 antibodies in any of the rescue treatments, without achieving CR.
5. Patients with classic Hodgkin's disease: 3. Primary refractory patients (after 1st line of treatment) and who do not achieve CR after rescue treatments that include brentuximab and anti-PDL1 antibodies.
6. Patients with anaplastic large cell T lymphoma (ALK + and ALK -) and peripheral T lymphoma (NOS and angioimmunoblastic): 1. CD30 expression (determined by immunohistochemistry) in > 90% of tumor cells for peripheral T lymphoma
7. Patients with anaplastic large cell T lymphoma (ALK + and ALK -) and peripheral T lymphoma (NOS and angioimmunoblastic): 2. Age 18 years or older
8. Patients with anaplastic large cell T lymphoma (ALK + and ALK -) and peripheral T lymphoma (NOS and angioimmunoblastic): 3. Patients in relapse after an autologous transplant of hemopoietic progenitors.
9. Patients with anaplastic large cell T lymphoma (ALK + and ALK -) and peripheral T lymphoma (NOS and angioimmunoblastic): 4. Primary refractory patients (after 1st line of treatment that includes anthracycline) who do not achieve CR after rescue chemotherapy (type ESHAP, ICE, DHAP, Gemox or brentuximab vedotin).
10. General status according to ECOG scale: 0-1.
11. FEV1 > 39%; DLCO and FVC > 39% of normal theoretical values.
12. Absence of significant ventricular dysfunction: left ventricular ejection fraction >40%.
13. Total bilirubin and transaminases < 3 times the maximum normal value, unless attributable to lymphoma.
14. Creatinine < 2 times the maximum normal value and clearance > 40 mL/min.
15. Negative serology for HIV, HBV and HCV. In the case of patients with positive serology for HBV or HCV, they must have a viral load of 0 measured by quantitative PCR
16. Absence of active, clinically relevant bacterial or viral infection. A diagnostic test for influenza virus, respiratory syncytial (nasopharyngeal aspirate) and SarsCov2 must be performed in ALL patients, prior to starting treatment, with a negative result.

Exclusion criteria 19

1. General condition determined according to ECOG scale: 2-4.
2. Previous allogeneic hemopoietic transplant within 12 weeks prior to screening.
3. Presence of acute graft-versus-receptor disease (GVHD) or chronic GVHD requiring immunosuppressive treatment of any type
4. Active HBV or HCV infection
5. HIV infection
6. Active, clinically relevant bacterial, fungal or viral infection.
7. Active infiltration of the CNS by lymphoma. Previous infiltration by lymphoma is not exclusive if there is demonstration of absence of disease in the CNS prior to treatment.
8. Abnormal kidney and liver functions, with creatinine and/or bilirubin levels 2 and 3 times higher than the normal limit value, respectively, except when the alterations are attributable to lymphoma (only in the case of liver alliteration).
9. Patients with decreased ventricular ejection fraction (FEV) (less than 40%), symptomatic heart failure, or both
10. Presence of cirrhosis or active hepatitis due to HBV or HCV virus
11. Patients with concomitant severe neurological or psychiatric illness
12. Presence of active autoimmune or rheumatologic disease requiring systemic treatment with any immunosuppressant (including prednisone at any dose).
13. Pneumopathy of any type that causes a DLC <39%
14. Major surgery in the 6 weeks prior to the start of inclusion.
15. Any concomitant antineoplastic treatment.
16. Pregnant or lactating patients.
17. Previous or concurrent neoplasms. Except: basal cell or squamous cell carcinoma, history of carcinoma in situ with previous curative treatment, solid neoplasia with complete resection and in remission for >3 years.
18. Before starting lymphoapheresis, all of the following requirements must be met: - absolute lymphocyte count in peripheral blood > 100/ml. - absence of chemotherapy treatment in the previous 2 weeks. - absence of treatment with brentuximab in the last 2 months. - absence of treatment with anti-PD1 in the previous 6 weeks. - absence of treatment with corticosteroids (any dose), with the exception of hydrocortisone (maximum 10 mg/m2). - absence of treatment with G-CSF/GM-CSF. - absence of treatment with any immunosuppressant (calcineurin inhibition, mycophenolate, rapamycin, anti-IL-6 or IL-6R antibodies, methotrexate) in the previous 2 weeks.
19. Before starting lymphodepleting chemotherapy, the following requirements (all) must be met: - absence of clinically relevant active bacterial, fungal or viral infection. Viral infections that must be evaluated before starting chemotherapy are: influenza virus, respiratory syncytial virus and SarsCov2, using a nasopharyngeal aspirate whose result is negative. - absence of antineoplastic treatment in the previous 2 weeks. - absence of treatment with corticosteroids (any dose), with the exception of hydrocortisone (maximum 10 mg/m2). - absence of treatment with G-CSF/GM-CSF. - absence of treatment with any immunosuppressant (calcineurin inhibition, mycophenolate, rapamycin, anti-IL-6 antibodies, methotrexate) in the previous 2 weeks.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose-limiting toxicity (DLT): the proportion of patients with DLT in the first month after infusion of HSP-CAR30 cells will be calculated, for each dose, together with the 95% confidence interval.
2. Safety: Data on the type and frequency of AEs will be collected for each dose level, starting from the infusion of HSP-CAR30 cells and up to 30 days thereafter.
3. Answer: the percentage of responses (RC, RP and RG) will be analyzed according to RECIL 2017 criteria and its 95% confidence interval will be calculated. Only patients who receive the infusion of HSP-CAR30 cells will be evaluable for response. In no case will patients who do not present detectable disease by PET-CT (patient in CR), determined in the 30 days prior to the infusion of HSPCAR30 cells, be considered for response analysis.

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

UICEC Sant Pau

Public contact point

Organisation

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

Contact name

UICEC Sant Pau

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 9 files

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

Application history

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