Author:
Kekre Natasha,Hay Kevin A.,Webb John R.,Mallick Ranjeeta,Balasundaram Miruna,Sigrist Mhairi K.,Clement Anne-Marie,Nielsen Julie S.,Quizi Jennifer,Yung Eric,Brown Scott D.,Dreolini Lisa,Waller Daniel D.,Smazynski Julian,Gierc Nicole S.,Loveless Bianca C.,Clark Kayla,Dyer Tyler,Hogg Richard,McCormick Leah,Gignac Michael,Bell Shanti,Chapman D. Maria,Bond David,Yong Siao,Fung Rachel,Lockyer Heather M.,Hodgson Victoria,Murphy Catherine,Subramanian Ana,Wiebe Evelyn,Yoganathan Piriya,Medynski Liana,Vaillan Dominique C.,Black Alice,McDiarmid Sheryl,Kennah Michael,Hamelin Linda,Song Kevin,Narayanan Sujaatha,Rodrigo Judith A.,Dupont Stefany,Hawrysh Terry,Presseau Justin,Thavorn Kednapa,Lalu Manoj M.,Fergusson Dean A.,Bell John C.,Atkins Harold,Nelson Brad H.,Holt Robert A.
Abstract
Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.
Subject
Immunology,Immunology and Allergy