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

This clinical trial is a Phase I/II, pilot, open-label, national, prospective, multicentre, non-randomised, open-label study to evaluate the safety and efficacy of TranspoCART19 in patients with relapsed/refractory B-lymphoma whose prognosis is less than 2 years.

Phase I: Dose escalation phase with a classic 3+3 design, in which three dose levels of TranspoCART19 will be evaluated: 1 x 106 cells/kg, 3 x106 cells/kg and 5 x 106 cells/kg. The maximum number of patients included in this phase will be 18.

Phase II: an expansion cohort with the maximum tolerated dose (MTD) determined in Phase I.

Patients will be included in the expansion cohort up to a total of 27, including Phase I patients.

Inclusion criteria

• Patients diagnosed with relapsed or refractory B-cell lymphoma (Diffuse large B-cell lymphoma, 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).
• Age over 18 years and under 80 years.
• 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).
• Adequate bone marrow haematopoietic reserve.
• Life expectancy of at least 2 months.
• Adequate venous access for lymphapheresis. Absence of contraindications for lymphapheresis.
• Signed informed consent (patient or legal guardian).

Exclusion criteria

• Patients who, in the opinion of a physician, may benefit from other approved potentially curative therapeutic options, including commercial CAR-Ts.
• Treatment with any experimental or non-commercialised substance in the four weeks prior to recruitment, or who are actively participating in another therapeutic clinical trial.
• Diagnosis of another neoplasm, past or present. Patients who have been in complete remission for more than 3 years, or with a history of non-melanoma skin cancer or completely resected carcinoma in situ may be included. A current or previous history of clonal T-lymphocytes is also an exclusion criterion.
• Early relapse after allogeneic haematopoietic stem cell transplantation (less than 3 months for lymphapheresis, less than 6 months for TranspoCART19 infusion) or patients on active immunosuppressive treatment for graft-versus-recipient disease (corticosteroids or other systemic immunosuppressants).
• Active infection requiring systemic medical treatment.
• HIV infection.
• Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric illnesses that in the opinion of the investigator pose a risk to the patient.
• Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBcore antibodies, a hepatitis B virus DNA test will be required, and if the result is positive the patient will be excluded.
• Positive serology for hepatitis C virus (HCV), defined as a positive test for anti-HCV antibodies that is confirmed by Recombinant immunoblot assay (RIBA).
• Severe organ involvement, defined as cardiac ejection fraction <40%; diffusing capacity of the lungs for carbon monoxide (DLCO) <40%; calculated glomerular filtration rate <30 ml/min; baseline O2 saturation <92%; bilirubin > 2 times upper limit of normal (unless due to Gilbert's syndrome) or transaminases > 2.5 upper limit of normal.
• Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test at screening.
• Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective methods of contraception* from the start of the study until the end of the study.
• 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.
• Need to take glucocorticoids chronically in doses greater than 10 mg/day of prednisone (or equivalent) or other chronic immunosuppressants.
• Previous anti-CD19 CAR-T therapy. Previous treatment with other anti-CD19 strategies is permitted, provided that CD19 expression has been confirmed in the tumour biopsy.
• Hypersensitivity to the active substance or to any of the excipients.