Clinical Trial 20592

Study Title

An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating the Safety and Efficacy of AUTO1, a CAR T Cell Treatment Targeting CD19, in Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia

Summary

This is a Phase Ib/II study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (ALL).

Objective

Phase Ib Primary Objective: -to evaluate the safety of AUTO1 Phase II: Primary Objective -to evaluate the clinical efficacy of AUTO1 Phase Ib Secondary Objectives: -to evaluate the feasibility of manufacturing and administering AUTO1 -to evaluate the clinical efficacy of AUTO1 -to evaluate the expansion and persistence of AUTO1 Phase II Secondary Objectives: -to evaluate the clinical efficacy of AUTO1 -to assess the safety and tolerability of AUTO1 -to evaluate the feasibility of manufacturing and administering AUTO1 -to evaluate the expansion and persistence of AUTO1 -to evaluate the duration of B cell aplasia -to evaluate Patient Reported Outcome and Quality of Life -to evaluate health care resource utilization for the management of AUTO1 related toxicity Exploratory Objectives: -to determine the proportion of patients who achieve MRD-negative CR using next generation sequencing -to determine ORR and DoR in patients who have received prior blinatumomab -to determine ORR in patients with ≤20% and >20% blasts prior to pre-conditioning as assess by IRRC -to determine the time course and magnitude of cytokine release evaluated using an appropriate assay -to assess antibody and/or T cell mediated immune responses against AUTO1 -to characterize the relationship between the CAR-T cell phenotype/genomics and persistence in vivo -seek any relationship between parameters of activity and tumor burden (e.g. % blast cells in BM, or EM site), level of CD19 expression (flow cytometry or immunohistochemistry [IHC]), CAR T cell phenotype -seek any relationship between incidence and severity of CRS, neurotoxicity, or other toxicity and tumour burden (e.g. % blast cells in BM, or EM site), level of CD19 expression (IHC or flow cytometry), CAR T Cell phenotype -to evaluate CSF for cytokine and CAR T cell levels in patients experiencing neurologic toxicity whenever feasible