CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies

Abstract

We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19⁺ malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4-5 × 10⁶ ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin's lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%-67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%-88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583.

Keywords: A3B1; ALL; ARI-0001; CART-cells; CD19; NHL.

Graphical abstract

Figure 1

Consort Diagram of Patients Included in the CART19-BE-01 Trial

Figure 2

Clinical Outcome of Patients with Acute Lymphoblastic Leukemia (A–D) Progression-free survival (A), overall survival (B), in vivo survival of ARI-0001 cells, as measured by persistence of B cell aplasia (C), and procedure-related mortality (D) of patients with acute lymphoblastic leukemia belonging to the modified full analysis set (n = 38) according to type of administration (cohorts 1 and 2 versus cohort 3).

Figure 3

Swimmer Plot of Patients with Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia Belonging to the Modified Full Analysis Set (n = 9) Green denotes complete remission, blue denotes partial remission, and red denotes refractory disease or disease progression. Sharp edges denote “alive at last follow-up,” round edges denote “dead at last follow-up.”