This is a phase I, open label study to evaluate the safety, identify the recommended dose (RD) and obtain preliminar evidence of the efficacy of allogeneic, CD19-directed Chimeric Antigen Receptor T (alloCAR-T) cells in pediatric and young adults patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL).
Relapse after alloHSCT OR
Relapsed/refractory disease, with failure of frontline therapy and at least 2 rescue strategies, including CD19/CD22-directed monoclonal antibody and availability of a fully matched related donor.
CD19+ count ≥ 50 cells/mcl and/or Minimal Residual Disease (MRD) ≥ 10^-4.
Voluntary informed consent. For subjects < 18-years old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
Pregnant or lactating women.
Severe, uncontrolled active intercurrent infections.
HIV, or active HCV and/or HBV infection.
Life-expectancy < 6 weeks or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy.
Single group
CD19-CAR_Lenti_ALLO
DrugBiological/Vaccine: CD19-CAR\_Lenti\_ALLO A single infusion of CD19-CAR\_Lenti\_ALLO on Day 0
Safety and establishment of Dose limited Toxicity (DLT) of the infusion of CD19-CAR_Lenti_ALLO cells in pediatric and young adults patients affected by relapsed/refractory BCP-ALL in each dose level
DLT is defined as any of the following events: (1) Grade III-IV GvHD refractory to first and second line treatment and chronic GvHD refractory to first and second-ine treatment; (2) any grade 4 non-hematologic toxicity; (3) grade 4 reactions realted to anti-alloCART infusion; (4) death related to alloCART infusion. The Maximum Tolerated Dose/Recommended Dose (MTD/RD) of CD19-CAR\_Lenti\_ALLO to be evaluated for efficacy in the phase II extension will be defined as the highest dose level at which \<33% of patients (no more than 1 out of 6) experience DLT.
To estimate the rate of occurrence of acute GvHD
The occurrence of acute GvHD will be recorded for every patient
To estimate the severity of acute GvHD (according to the MAGIC criteria)
The severity of acute GvHD will be recorded for every patient
To estimate the rate of occurrence of chronic GvHD
The occurrence of chronic GvHD will be recorded for every patient
To estimate the severity of chronic GvHD (according to the NIH 2014 criteria)
The severity of chronic GvHD will be recorded for every patient
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