The prognosis of patients with relapsed/refractory acute lymphoid leukemia (R/R ALL) is very poor with conventional treatment. In the last decade, several institutions have developed a new kind of gene/cell therapy called targeting the CD19 antigen (CART19 cells). Results with CART19 cells have been impressive and the FDA recently approved one of these CART19 cell products (tisa-cel) for pediatric or young adults with R/R ALL, although with a price tag of $475,000 per patient. We have developed a new construct incorporating our own anti-CD19 monoclonal antibody (A3B1) plus CD8, 4-1BB and CD3z modules, cloned it into a 3rd generation lentiviral vector, and transduced T-cells after CD3/CD28 activation (ARI-0001 cells). Our academic option can be manufactured for around 60.000 euros using an automated system (CliniMACS Prodigy, Miltenyi) that requires little user interaction, thus ensuring reproducibility while minimizing contamination. In May 2017 the Spanish Agency for Medicines (AEMPS) approved our investigational new drug (nº 16-187) and pilot clinical trial (CART19-BE-01, clinicaltrials.gov NCT03144583). This trial has already completed the pre-specified recruitment of 10 patients and the primary endpoint of this trial (safety) has been already met since only one patient has developed ARI-0001-related severe adverse events. The aim of this new trial (CART19-BE-02) is to prove the efficacy of ARI-0001 cells in patients with R/R ALL in the context of a multi-center phase II study. We have calculated a sample size of 31 patients assuming a minimum 6-month PFS of 65% for ARI-0001 cells. MRD will be measured through flow cytometry and NGS. In this new project we plan to expand this cell therapy program to 9 new institutions from different Spanish regions, with the aim of gaining sufficient experience for a successful Hospital Exemption application in the future, this allowing participating centers to carry on treating patients outside clinical trials.

receptor de antígeno quimérico
CD19
leucemia linfoblástica aguda
vector lentiviral
CliniMACS Prodigy
secuenciación de nueva generación
prueba de medicina de precisión
célula ARI-0001