This study aims at evaluating the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B-cell surface antigen CD19, following administration of lymphodepleting chemotherapy regimen, in children and adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B- ALL) or aggressive B-cell Non-Hodgkin lymphoma (B-NHL). The phase II extension is aimed at testing the efficacy of the treatment at the optimal dose defined in the phase I. In addition, the investigators hypothesize that it is feasible to successfully manufacture CAR T cells to meet the established release criteria at a maximum target dose of 3.0 x 10\^6 cells/kilogram recipient total body weight in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Fresh peripheral blood mononuclear cells are manufactured to obtain CD19-CAR\_Lenti T cell, second generation CAR T cells incorporating the 4-1BB costimulatory domain. The fresh product is infused following lymphodepletion chemotherapy at a dose of 1.0-3.0x10\^6 CAR+ cells/kg.
IRCCS Ospedale Pediatrico Bambino Gesù
Roma, Italy
Phase I - Identification of dose limiting toxicities (DLTs) and recommended dose (RD)
Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 5.0
Time frame: 4 weeks after CAR T cell infusion
Phase I - Identification of recommended dose (RD)
The recommended dose of CD19-CAR\_Lenti will be defined as the maximum tolerated dose (MTD) or the highest dose studied, if an MTD is not reached.
Time frame: 4 weeks after CAR T cell infusion of the last patient in the last dose level
Phase II - Efficacy
Bone marrow morphological and minimal residual disease complete remission rate at day 28 after infusion for BCP-ALL; Overall Response Rate (CR, CRi, PR and SD) at day 28, day 90 and day 180 after CAR T cells infusion
Time frame: Up to 6 months after CAR T cell infusion
Relapse Rate (RR)
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Disease-Free Survival (DFS)
Time frame: Up to 2 years
In vivo persistence/expansion of infused CAR T cell
Detection of infused CAR T cell in the peripheral and bone marrow blood
Time frame: Up to 2 years
Cytokine profiling
Define serum cytokine profile (Th1/Th2) after T cell infusion and correlation with cytokine release syndrome (CRS)
Time frame: Up to 10 days after CAR T cell infusion
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