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

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

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Publication Details

Journal
Blood Cancer Journal
Published
2025-04-24
DOI
https://doi.org/10.1038/s41408-025-01279-9
Citations
9
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
9.41
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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

Sumeet Mirgh, Aalia Khan, Steven L. Highfill, Akanksha Chichra et al.
9 citations
Blood Cancer Journal
CAR-T cell therapy research
9.41
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

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

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

Blood Cancer JournalVol. 15(1)
National Institutes of Health (US), Indian Institute of Technology Bombay (IN), Homi Bhabha National Institute (IN), Tata Memorial Hospital (IN), National Cancer Institute (US), Immune Regulation (United Kingdom) (GB), Center for Cancer Research (US), Advanced Centre for Treatment, Research and Education in Cancer (IN), Jawaharlal Institute of Post Graduate Medical Education and Research (IN)
Good health and well-being
Openalex Percentile: Top 2%
CAR-T cell therapy research
9.41
DOIOpen Access PDFOpenAlex
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