Dataset Information

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.

SUBMITTER: Ortiz-Maldonado V

PROVIDER: S-EPMC7854276 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Ortíz-Maldonado Valentín V Rives Susana S Castellà Maria M Alonso-Saladrigues Anna A Benítez-Ribas Daniel D Caballero-Baños Miguel M Baumann Tycho T Cid Joan J Garcia-Rey Enric E Llanos Cristina C Torrebadell Montserrat M Villamor Neus N Giné Eva E Díaz-Beyá Marina M Guardia Laia L Montoro Mercedes M Català Albert A Faura Anna A González E Azucena EA Español-Rego Marta M Klein-González Nela N Alsina Laia L Castro Pedro P Jordan Iolanda I Fernández Sara S Ramos Federico F Suñé Guillermo G Perpiñá Unai U Canals Josep M JM Lozano Miquel M Trias Esteve E Scalise Andrea A Varea Sara S Sáez-Peñataro Joaquín J Torres Ferran F Calvo Gonzalo G Esteve Jordi J Urbano-Ispizua Álvaro Á Juan Manel M Delgado Julio J

Molecular therapy : the journal of the American Society of Gene Therapy 20200920 2

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 ...[more]

PMID: 33010231

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Project description:BackgroundFor CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy.MethodsNineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4-1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0-18.0 × 105/kg).ResultshCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12-18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity.ConclusionsHumanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal.Trial registrationChinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.

Dataset Information

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

Publications

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

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