Treatment of Relapsed or Refractory B-cell Lymphoma With Chimeric Antigen Receptor (CAR) T-cell Therapy Produced by a New Technology

Inclusion Criteria:

1. Patients diagnosed with relapsed or refractory B-cell lymphoma (Diffuse large B-celllymphoma, Primary diffuse large B-cell lymphoma of the Central Nervous System (CNS),Mantle cell lymphoma, Follicular lymphoma grades 1, 2 or 3a or Marginal lymphoma,including splenic, nodal and MALT).

2. Age over 18 years and under 80 years.

3. Functional status Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.Patients with ECOG 2 may be included if motivated by haematological disease (Annex 3).

4. Adequate bone marrow haematopoietic reserve.

5. Life expectancy of at least 2 months.

6. Adequate venous access for lymphapheresis. Absence of contraindications forlymphapheresis.

7. Signed informed consent (patient or legal guardian).

Exclusion Criteria:

1. Patients who, in the opinion of a physician, may benefit from other approvedpotentially curative therapeutic options, including commercial CAR-Ts.

2. Treatment with any experimental or non-commercialised substance in the four weeksprior to recruitment, or who are actively participating in another therapeuticclinical trial.

3. Diagnosis of another neoplasm, past or present. Patients who have been in completeremission for more than 3 years, or with a history of non-melanoma skin cancer orcompletely resected carcinoma in situ may be included. A current or previous historyof clonal T-lymphocytes is also an exclusion criterion.

4. Early relapse after allogeneic haematopoietic stem cell transplantation (less than 3months for lymphapheresis, less than 6 months for TranspoCART19 infusion) orpatients on active immunosuppressive treatment for graft-versus-recipient disease (corticosteroids or other systemic immunosuppressants).

5. Active infection requiring systemic medical treatment.

6. HIV infection.

7. Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic,gastrointestinal, endocrine, pulmonary, neurological or psychiatric illnesses thatin the opinion of the investigator pose a risk to the patient.

8. Positive serology for hepatitis B, defined as a positive test for HBsAg. Inaddition, if the patient is HBsAg negative but has anti-HBcore antibodies, ahepatitis B virus DNA test will be required, and if the result is positive thepatient will be excluded.

9. Positive serology for hepatitis C virus (HCV), defined as a positive test foranti-HCV antibodies that is confirmed by Recombinant immunoblot assay (RIBA).

10. Severe organ involvement, defined as cardiac ejection fraction <40%; diffusingcapacity of the lungs for carbon monoxide (DLCO) <40%; calculated glomerularfiltration rate <30 ml/min; baseline O2 saturation <92%; bilirubin > 2 times upperlimit of normal (unless due to Gilbert's syndrome) or transaminases > 2.5 upperlimit of normal.

11. Pregnant or lactating women. Women of childbearing age should have a negativepregnancy test at screening.

12. Women of childbearing age, including those whose last menstrual cycle was in theyear prior to screening, who are unable or unwilling to use highly effective methodsof contraception* from the start of the study until the end of the study.

13. Men who are unable or unwilling to use highly effective methods of contraception*from the start of the study until the end of the study.

14. Need to take glucocorticoids chronically in doses greater than 10 mg/day ofprednisone (or equivalent) or other chronic immunosuppressants.

15. Previous anti-CD19 CAR-T therapy. Previous treatment with other anti-CD19 strategiesis permitted, provided that CD19 expression has been confirmed in the tumour biopsy.

16. Hypersensitivity to the active substance or to any of the excipients.