Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study

Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study

Abstract Chimeric Antigen Receptor-T (CAR-T) cell therapy is effective for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) but is not universally available. We developed a novel humanized CD19-directed CAR-T (HCAR19) approved for Phase 1/1b/2 trials. Patients aged 3–25 years were enro...

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Main Authors: Gaurav Narula, Swaminathan Keerthivasagam, Hasmukh Jain, Sachin Punatar, Akanksha Chichra, Chetan Dhamne, Prashant Tembhare, Papagudi Ganesan Subramanian, Nikhil Patkar, Minal Poojary, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Albeena Nisar, Deepali Pandit, Khushali Pandit, Alka Dwivedi, Atharva Karulkar, Ankesh Kumar Jaiswal, Aalia Khan, Shreshtha Shah, Afrin Rafiq, Moumita Basu, Juber Pendhari, Sweety Asija, Ambalika Chowdury, Ankit Banik, Nirmalya Roy Moulik, Shyam Srinivasan, Shilpushp Bhosle, Sumathi Hiregoudar, Shashank Ojha, Lingaraj Nayak, Jayshree Thorat, Bhausaheb Bagal, Manju Sengar, Navin Khattry, Shripad Banavali, Steven Highfill, Nirali N. Shah, Rahul Purwar
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01279-9
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Summary:Abstract Chimeric Antigen Receptor-T (CAR-T) cell therapy is effective for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) but is not universally available. We developed a novel humanized CD19-directed CAR-T (HCAR19) approved for Phase 1/1b/2 trials. Patients aged 3–25 years were enrolled with r/r B-ALL and ineligible for allogeneic stem cell transplant. Lymphodepletion utilized standard-dose fludarabine and cyclophosphamide. A 3 + 3 design testing 3 dose-ranges was used to determine Phase-2 Dose (P2D): Dose-A, 1 × 106 HCAR19 cells/kg, Dose-B, 3–5 × 106/kg, and Dose-C, 10–15 × 106/kg. Primary endpoint was overall response rate (ORR) at day-30 on bone-marrow flow-cytometry. From May-2021 to September-2023 12 patients [median age-14 (range: 5–24) years] were enrolled with median bone marrow blasts 19.5% at screening. Cytokine release syndrome occurred in 10 (83%) patients, predominantly Grades 1–2, and Grade-2 immune-cell associated neurotoxicity (ICANS) in 1. All patients had Grade-3 cytopenia. ORR was 91.7% (11/12), complete response (CR) in 8 (66.7%) and partial response in 3 (25%). Seven of 8 CRs were at Dose-levels B and C, all of which were sustained till 12 months follow-up. Patients who received dose levels below 3 × 106/kg, or did not achieve CR, had early loss of response or rapid progression. HCAR19 demonstrated safety, manageable toxicity, and durable remissions. and P2D was determined as 5–10 × 106 HCAR19-cells/kg. Clinical trial registration The study is registered in the Clinical Trials Registry- India (CTRI/2021/05/033348 and CTRI/2023/03/050689).
ISSN:2044-5385

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