Analysis of a Global Registration Trial of the Efficacy and Safety of CTL019 in Pediatric and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

作者：Stephan A. Grupp, Theodore W. Laetsch, Jochen Buechner, Henrique Bittencourt, Shannon L. Maude, Michael R. Verneris, Gary Douglas Myers, Michael W. Boyer, Susana Rives, Barbara De Moerloose, Eneida R. Nemecek, Krysta Schlis, Paul L. Martin, Muna Qayed, Peter Bader, Hidefumi Hiramatsu, Françoise Méchinaud, Gregory A. Yanik, Christina Peters, Andrea Biondi, André Baruchel, Nicolas Boissel, Joerg Krueger, Carl H. June, Kapildeb Sen, Yiyun Zhang, Karen E. Thudium, Patricia A. Wood, Tetiana Taran, Michael A. Pulsipher · 发表于：Blood · 年份：2016 · DOI：10.1182/blood.v128.22.221.221 · 被引用次数：83 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research

Abstract A single-center trial of CD19 directed, lentiviral transduced chimeric antigen receptor (CAR) T cells (CTL019) for relapsed and refractory (r/r) B-ALL pediatric patients showed rates of CR >90% with prolonged CAR T cell persistence/CR without further therapy in the majority of patients infused (Maude NEJM 2014). We report here the feasibility, safety and efficacy of the first multicenter global pivotal registration CAR T cell trial. Features of this trial include: i) the first trial in which industry-manufactured cells were provided to all patients; ii) enrollment across 25 centers in the US, EU, Canada, Australia, and Japan; iii) successful transfer and manufacturing of cells in a global supply chain; and iv) successful implementation of cytokine release syndrome (CRS) management across a global trial. All patients had CD19 positive B-ALL with morphologic marrow tumor involvement at registration (>5% blasts), and were either primary refractory; chemo-refractory after first relapse, relapsed after second line therapy; or ineligible for allogeneic SCT. CTL019 was manufactured from patient PBMC under GMP conditions in the US, at a centralized "sponsor-owned" manufacturing facility, and supplied to all sites. The primary endpoint of overall remission rate (CR+CRi) within 3 months and secondary endpoints (EFS, DOR, OS and safety) were assessed by an independent review committee. Based on preliminary data as of March 2016, 57 patients were enrolled. There were 3 manufactu...