Journal Article

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

Ojha, Shashank, Hiregoudar, Sumathi, Rafiq, Afrin, Dhamne, Chetan, Jain, Hasmukh, Thorat, Jayshree, Highfill, Steven, Purwar, Rahul, Khan, Aalia, Moulik, Nirmalya Roy, Keerthivasagam, Swaminathan, Poojary, Minal, Subramanian, Papagudi Ganesan, Jaiswal, Ankesh Kumar, Bhosle, Shilpushp, Banavali, Shripad, Shah, Shreshtha, Gokarn, Anant, Chowdury, Ambalika, Srinivasan, Shyam, Sengar, Manju, Karulkar, Atharva, Punatar, Sachin, Pandit, Deepali, Banik, Ankit, Asija, Sweety, Bagal, Bhausaheb, Shah, Nirali N., Mirgh, Sumeet, Patkar, Nikhil, Nayak, Lingaraj, Khattry, Navin, Nisar, Albeena, Tembhare, Prashant, Chichra, Akanksha, Jindal, Nishant, Dwivedi, Alka, Pandit, Khushali, Basu, Moumita, Narula, Gaurav, Pendhari, Juber

2025

Overview

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 × 10 6 HCAR19 cells/kg, Dose-B, 3–5 × 10 6 /kg, and Dose-C, 10–15 × 10 6 /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 × 10 6 /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 × 10 6 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).

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/1 / 13/21 / 13/31 / 13/44 / 631/67/1059/602 / 692/699/67/1990/283/2125 / Adolescent / Adult / Antigens, CD19 - immunology / Biomedical and Life Sciences / Biomedicine / Cancer Research / Child / Child, Preschool / Female / Hematology / Humans / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Leukemia / Male / Oncology / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy / Receptors, Chimeric Antigen - immunology / Young Adult