Clinical Trial 19481

Study Title

Phase I, Open Label Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART123 (Allogeneic Engineered T Cells Expressing anti-CD123 Chimeric Antigen Receptor), Administered in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Summary

Phase I, first-in-human, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of UCART targeting CD123 in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of one infusion of UCART123 and determine the Maximum Tolerated Dose (MTD).

Objective

Primary:  To assess the safety and tolerability of Universal Chimeric Antigen Receptor (CAR) T-cells targeting Cluster of Differentiation (CD) 123 (UCART123) administered to patients with relapsed/refractory and newly diagnosed highrisk acute myeloid leukemia (AML), and  To determine the Recommended Phase 2 Dose (RP2D) of UCART123. Secondary:  To assess the efficacy of UCART123 in relapsed or refractory AML patients and in patients with newly diagnosed, untreated AML (as defined by World Health Organization [WHO] criteria, [Arber et al., 2016]) who meet criteria for the European Leukemia Net (ELN) adverse genetics prognostic group (Döhner et al., 2016; Röllig et al., 2011). Exploratory:  To characterize the expansion, trafficking, and persistence of UCART123 after infusion by assessing the kinetics and characteristics of UCART123 at different time-points, in blood and bone marrow;  To assess cytokine, growth factor, and C-reactive protein levels after UCART123 infusion;  To investigate the development of an UCART123 generated immune response;  To investigate the potential relationship between baseline levels of CD123 expression and clinical outcome;  To assess the impact of UCART123 on leukemia stem cells, hematopoietic stem cells (HSCs), and progenitor cells;  To confirm the absence of replication competent lentivirus in blood;  To assess the impact of UCART123 on the tumor cell population by targeted sequencing; and  To monitor immune cell depletion and reconstitution post lymphodepletion and UCART123.