UHKT-CAR19-01Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells (CART19) in Patients with Relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma. a Dose Escalation, Open-label, Phase I Study.

Fecha de inicio: 2 de junio de 2021

Inclusion Criteria: 1. Patient with refractory or relapsing CD19 positive B-ALL or B-NHL defined as: 1. B-ALL refractory to treatment or in the second or subsequent relapse (hematological OR molecular), OR 2. B-NHL refractory to treatment or in first relapse ineligible for autologous stem cell transplantation (ASCT) or in second to fourth relapse, OR 3. B-ALL or B-NHL relapsing after autologous or allogeneic hematopoietic cell transplantation (HCT). 2. CD19 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry. 3. Age ≥18 years and ≤ 80 yearss. 4. Patient able to understand and sign informed consent. 5. Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1. General Exclusion Criteria: 1. Known hypersensitivity to any component of the Investigational Medicinal Product (IMP). 2. Autologous or allogeneic HCT in 3 months prior to IMP administration. 3. Severe, uncontrolled active infection. 4. Life expectancy \< 6 weeks. 5. Parenchymal central nervous system involvement. 6. Respiratory insufficiency (need for oxygen therapy). 7. Significant liver impairment: bilirubin \> 50 µmol/L, AST or ALT \> 4times normal upper limit. 8. Acute kidney injury with serum creatinine \> 180 µmol/L, oliguria or need for acute dialysis. 9. Heart failure with EF \< 30% by echocardiography. 10. Presence of active grade 3-4 acute GvHD. 11. Serious uncontrolled neurological comorbidity. 12. Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose. 13. Women: pregnancy or breast-feeding. 14. Subjects of fertile age, unless permanent sexual abstinence is their lifestyle choice: * female patients of childbearing potential not willing to use a highly effective method of contraception during the study, * male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a highly effective method of contraception during the study. Exclusion criteria to Procurement of IMP manufacture starting material 1. Severe uncontrolled active infection. 2. Positive test results for HIV1/2, Hepatitis B/C and lues. 3. Concurrent or recent prior therapies before apheresis: * Autologous or allogeneic hematopoietic cell transplantation within 12 weeks. * Clofarabine, Fludarabine, Alemtuzumab within 8 weeks. * Donor lymphocyte infusions within 4 weeks. * Pegylated asparaginase within 4 weeks. * Maintenance chemotherapy within 2 weeks. * Long-acting Granulocyte Colony Stimulating Factor (G-CSF) within 2 weeks. * Vincristine within 2 weeks. * Intrathecal methotrexate within 1 week. * Granulocyte Colony Stimulating Factor (G-CSF) within 5 days. * Therapeutic dose of corticosteroids within 3 days. * Short-acting cytostatics within 3 days Exclusion criteria to IMP administration 1. Severe, uncontrolled active infections. 2. Life expectancy \< 6 weeks. 3. Parenchymal central nervous system involvement 4. Respiratory insufficiency (need for oxygen therapy). 5. Significant liver impairment: bilirubin \> 50 µmol/L, Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \> 4times normal upper limit. 6. Acute kidney injury with serum creatinine \> 180 µg/L, oliguria or need for acute dialysis. 7. Heart failure with Ejection Fraction (EF) \< 30% by echocardiography. 8. Presence of active grade 3 - 4 acute GvHD 9. Serious uncontrolled neurological comorbidity.