Basket trial for B-cEll driven severe auToimmunE and aLoimmune diseases (chronic Graft vErsUs host diseaSe) treated with anti-CD19 CAR T-cell thErapy

Condition studied

Dermatomyositis/Polymyositis (DM/PM), Systemic Sclerosis (SSc), Neuromyelitis Optica (NMOSD), ANCA-associated vasculitis (AAv), Myasthenia Gravis (MG), Immune-Mediated Necrotizing Myopathy (IMNM), Systemic Lupus Erythematosus (SLE), chronic Graft-versus-Host Disease (cGVHD)

Investigational medicinal product(s)

Eligibility

Primary endpoint

a) Identification of the maximum tolerated dose/recommended dose defined as the DL of CD19-CART01 at which ≤33.3% of patients experience DLT, according to the 3+3 design, and assessment of the incidence and severity of CRS, ICANS, IEC-HS, and grade ≥2 infections within the first 4 weeks after infusion; assessment of the LICATS , the early/late N-ICAHT;, b) to assess the proportion of pts in whom the manufacturing process resulted in the production of sufficient transduced CD19-CART01 cells

Endpoint detail

a) Clinical efficacy will be measured with Overall Response Rate (ORR), in the absence of glucocorticoid and immunosuppressive therapy for at least 4 weeks,at weeks 24 and 48 after infusion for all disease considered (SLE, SSc, DM/PM, IMNM, AAv, MG and cGVHD)., b) Incidence,duration, and severityof hypogammaglobulinemia (according to CTCAE v.6.0) and incidence of peripheral blood B-cell depletion (0CD19+ cells/µL assessed by FACS) at week 48, c) Grade ≥2 (according to CTCAE v6.0) infections beyond the first 4 weeks after infusion and up to 48 weeks, d) Characterization of CD19-CART01 subpopulations in the drug product, andassessmentof in vivo expansion and persistence of CAR T-cells in the peripheral blood after CD19-CART01 infusion, e) Proportion of patients with ongoing glucocorticoids 24 weeks after CD19-CART01 infusion (defined as glucocorticoid-free state), f) Evaluation of QoL improvement at weeks 24 and 48 according to disease specific scales, scores, and questionnaires for all disease considered (SLE, SSc, DM/PM, IMNM, AAv, MG, NMOSD and cGVHD), g) Kinetics of levelsand incidence of seroconversion of disease-associated serum autoantibodies/biomarkers at weeks 24 and 48after infusion [...]