Single-center phase I/IIa study with CART cells produced using the anti-CD19 transposon technique (TranspoCART19) for patients with CD19+ acute lymphoblastic leukemia resistant or refractory to treatment

Prior treatment

• Concurrent and uncontrolled medical conditions including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, or psychiatric conditions that, in the opinion of the investigator, pose a risk to the patient.
• Women of childbearing potential, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective contraception* from baseline to completion.
• Treatment with any experimental or non-marketed substance within four weeks prior to enrollment, or actively participating in another therapeutic clinical trial.
• Previous treatment with CART (commercial or experimental).
• Overt central nervous system involvement (CNS-3) at the time of inclusion. Patients with a lesser degree (CNS-2) or CNS-3 who have responded to intrathecal chemotherapy will be eligible for inclusion.
• In the case of relapse after allogeneic transplantation, at least 3 months must have passed since the transplant for inclusion. Furthermore, the patient must have been off systemic immunosuppressants for at least 30 days to be eligible for inclusion.

Other illness

• HIV infecction
• Positive serology for hepatitis B, defined as a positive test for HBsAg. Additionally, if the patient is HBsAg negative but has anti-HBc antibodies, a hepatitis B virus DNA test will be required. If the result is positive, the patient will be excluded.
• Positive serology for hepatitis C, defined as a positive test for anti-HCV antibodies confirmed by RIBA.
• Diagnosis of another malignancy, 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.
• Isolated extramedullary involvement (i.e., in the absence of residual measurable disease in peripheral blood or bone marrow).
• Active immunosuppressive therapy for graft-versus-host disease and other conditions. The use of corticosteroids for leukemia control should be limited as much as possible at the time of enrollment and should be discontinued before the infusion of TranspoCART19 cells.
• Active infection requiring systemic medical treatment.

Lab values

• Severe organ involvement, defined as cardiac ejection fraction <40%; DLCO <40%; estimated glomerular filtration rate <30 ml/min; bilirubin >3 times the upper limit of normal (unless due to Gilbert's syndrome).

Age

• Pregnant or breastfeeding women. Women of childbearing age must have a negative pregnancy test during the screening phase.

Other

• Patients who, in the opinion of their physician, may benefit from other approved, potentially curative therapeutic options, including commercial CAR-T cells.
• Men who are unable or unwilling to use highly effective contraception* from the start of the study until its completion.

• Diagnosis of CD19+ acute lymphoblastic leukemia, with a prognosis of less than 2 years due to meeting one of the following conditions: ● Relapsed/refractory, not a transplant candidate (due to refractory disease or lack of a donor) ● Relapse after allogeneic transplant
• Measurable disease, understood as the presence of at least residual measurable disease by flow cytometry in bone marrow or peripheral blood at the time of inclusion.
• Age over 4 years and under 70 years.
• ECOG performance status 0-1. Patients with ECOG 2 may be included if due to hematologic disease (Appendix 1).
• Life expectancy greater than 3 months.
• Adequate venous access for lymphapheresis. No contraindications.
• Signing of informed consent (patient or legal guardian).