Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM)

Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia

Phase I, Open Label, Dose-escalation Study Followed by a Safety Expansion Part to Evaluate the Safety, Expansion and Persistence of a Single Dose of UCART19 (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor), Administered Intravenously in Patients With Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukaemia (B-ALL)

The study is in two parts: a dose escalation then a safety dose expansion. The purpose of the dose escalation part is to evaluate the safety and tolerability of ascending doses of UCART19 (dose-escalation part) given as a single infusion in patients with relapsed / refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL), to determine the maximum tolerated dose (MTD), the recommended dose and the lymphodepletion regimen. The purpose of the safety dose expansion is to assess the safety and tolerability of the RD for UCART19.

Dose escalation part: Dose Limiting Toxicities (DLTs) occurence. Dose expansion part: AE throughout the study.

Dose Escalation: Up to day 28 post first UCART19 infusion. Dose Expansion: From inclusion to Month 12

Proportion of patients in whom a response among molecular complete remission (mCR), morphologic complete remission (CR) and complete remission with incomplete blood count recovery (CRi)

From the time that response criteria are first met until the date of progression or death (whatever the reason of death), whichever occurs first, assessed up to Month 12

From the date of UCART19 administration until the date that response criteria are met, assessed up to Month 12

From the date of UCART19 administration until the date of progression or the date of death (whatever the reason of death), whichever occur first, assessed up to Month 12

Inclusion Criteria: Male or female participant Age ≥ 16 years Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL) who have exhausted alternative treatment options Estimated life expectancy ≥ 12 weeks (according to investigator's judgement) Eastern Cooperative Oncology Group (ECOG) performance status < 2 Exclusion Criteria: Previous treatment with gene or gene-modified cell therapy medicine products or adoptive T cell therapy Use of previous anti-leukemic therapy (including approved therapies and other investigational products) within 5 half-lives prior to UCART19 administration CD19 negative B-cell leukaemia Burkitt cell or mixed lineage acute leukaemia

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Benjamin R, Graham C, Yallop D, Jozwik A, Mirci-Danicar OC, Lucchini G, Pinner D, Jain N, Kantarjian H, Boissel N, Maus MV, Frigault MJ, Baruchel A, Mohty M, Gianella-Borradori A, Binlich F, Balandraud S, Vitry F, Thomas E, Philippe A, Fouliard S, Dupouy S, Marchiq I, Almena-Carrasco M, Ferry N, Arnould S, Konto C, Veys P, Qasim W; UCART19 Group. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020 Dec 12;396(10266):1885-1894. doi: 10.1016/S0140-6736(20)32334-5.

Benjamin R, Jain N, Maus MV, Boissel N, Graham C, Jozwik A, Yallop D, Konopleva M, Frigault MJ, Teshima T, Kato K, Boucaud F, Balandraud S, Gianella-Borradori A, Binlich F, Marchiq I, Dupouy S, Almena-Carrasco M, Pannaux M, Fouliard S, Brissot E, Mohty M; CALM Study Group. UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial. Lancet Haematol. 2022 Nov;9(11):e833-e843. doi: 10.1016/S2352-3026(22)00245-9. Epub 2022 Oct 10.

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