CARCIK-CD19

P1/2, N=29, Recruiting, Fondazione Matilde Tettamanti Menotti De Marchi Onlus | Not yet recruiting --> Recruiting

We conducted an academic phase I/II study (NCT03389035) with donor-derived anti-CD19 CAR T cells generated with Sleeping Beauty transposon (CARCIK-CD19) in B-ALL patients relapsed after alloHSCT... Through sc-RNAseq and spectral flow cytometry, we have characterized changes in the BM TME after CAR T cell therapy. Specifically, CAR T cells-mediated myeloid activation is associated with pathways of immune dysregulation that may dampen CAR T cell expansion and antagonize the effects of the therapy. Furthermore, these data support the hypothesis that transcriptomic interrogation can infer pathways relevant to the communication between CAR T cells and the TME.

P1/2, N=29, Not yet recruiting, Fondazione Matilde Tettamanti Menotti De Marchi Onlus

To overcome viral method's limitations in T cell engineering, our group developed an anti-CD19 CAR engineered Cytokine Induced Killer (CIK) cells through a Sleeping –Beauty (SB) trasposon-based platform (CARCIK-CD19)... In this study we demonstrated the efficacy, quality and safety of donor-derived SB-transfected CARCIK-CD22 with a remarkable anti-tumor activity in vitro and in in vivo mice models. Further experiments are ongoing forevaluating the activity of BAFFR CAR T cells in vivo. Overall, we demonstrated the feasibility of CARCIK-CD22 and CARCIK-BAFFR non-viral engineering to be employed in the context of multi-targeting approach to prevent and treat CD19 negative B-ALL relapses.

P1/2, N=21, Completed, Fondazione Matilde Tettamanti Menotti De Marchi Onlus | Active, not recruiting --> Completed | Trial completion date: Mar 2022 --> Dec 2022

Peripheral blood samples from patients enrolled in the CARCIK-CD19 clinical trial (Eudract N. 2017-000900-38) were used to assess and compare the stain indexes as well as the sensitivity and specificity of the different assays...This method clearly detected both Tisagenleleucel (Novartis) and Axicabtagene ciloleucel cells (Kite), demonstrating the broad applicability of the method to different CAR-T cells products... Three different CAR detection methods were compared with each other, the two indirect staining assays showed better results. The CD19-his and CD19-bio gave similar results, but CD19-his is more cost-effective compared to CD19-bio. CAR detection with CD19-his was validated with parallel real time PCR data.

Patients underwent fludarabine and cyclophosphamide-based lymphodepletion, before CARCIK-CD19 infusion. CR was defined as absence of leukemia in the BM at day 28. CARCIK-CD19 peak was defined as the maximum amount of CAR+

After lymphodepletion with Fludarabine (30 mg/m2/day x 4 days) and Cyclophosphamide (500 mg/m2/day x 2 days), patients received a single CARCIK-CD19 infusion. By univariate analysis, EFS was significantly associated with the % of blasts after lymphodepletion (≥ 5% vs <5%) (p=0.0245). Conclusions In this phase I/II dose-finding study, SB-engineered CAR T cells demonstrated an excellent safety profile with anti-leukemia activity in heavily pretreated patients with B-ALL relapsed after HSCT.

No abstract available

P2, N=35, Recruiting, Fondazione Matilde Tettamanti Menotti De Marchi Onlus

P1/2, N=21, Active, not recruiting, Fondazione Matilde Tettamanti Menotti De Marchi Onlus | Recruiting --> Active, not recruiting | Trial completion date: Apr 2021 --> Mar 2022 | Trial primary completion date: Dec 2020 --> Mar 2021