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 - Report - MDSpire

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

  • By

  • 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

  • April 24, 2025

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Humanized CD19-CAR-T Cells (Tali-cel™) in Pediatric Relapsed/Refractory B-ALL

Overview

This Phase I/Ib trial evaluated the safety and feasibility of talicabtagene autoleucel (Tali-cel™), an indigenously developed humanized CD19-directed CAR T-cell therapy, in pediatric and young adult patients with relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL). The study demonstrated successful manufacturing, regulatory approval, and administration of Tali-cel™ across three dose levels, establishing a foundation for determining the optimal Phase 2 dose.

Background

Pediatric B-ALL is highly curable with survival rates exceeding 90% in developed countries; however, outcomes remain poor for patients with relapsed or refractory disease. Immunotherapies such as BiTEs and ADCs have improved outcomes but are largely inaccessible in low- and middle-income countries. CAR T-cell therapy targeting CD19 has shown dramatic responses in r/r B-ALL but is often cost-prohibitive. To address this, an indigenous humanized CD19 CAR T-cell product, HCAR19 (Tali-cel™), was developed collaboratively in India and evaluated in a first-in-country Phase I/Ib trial for pediatric and young adult patients with r/r B-ALL.

Data Highlights

Dose LevelCAR T-Cells/kgTrial Phase
Dose-A1 × 106Phase I
Dose-B3–5 × 106Phase I
Dose-C10–15 × 106Phase 1b/2

Key Findings

  • The novel humanized CD19 CAR T-cell product (Tali-cel™) was successfully manufactured indigenously at IIT Bombay with clinical-grade quality.
  • The Phase I trial enrolled pediatric and young adult patients aged 3–25 years with r/r B-ALL who were ineligible for or unable to proceed with allogeneic stem cell transplant.
  • Three escalating dose levels (1 × 106, 3–5 × 106, and 10–15 × 106 CAR T-cells/kg) were tested to determine the optimal Phase 2 dose.
  • Regulatory approvals were obtained from multiple Indian oversight bodies, marking the first-in-country pediatric cell and gene therapy trial.
  • Patients received lymphodepletion chemotherapy with fludarabine and cyclophosphamide prior to CAR T-cell infusion.
  • The trial included bridging chemotherapy to control disease before CAR T-cell infusion.

Clinical Implications

Tali-cel™ represents a promising, cost-effective CAR T-cell therapy option developed within India, potentially improving access for pediatric and young adult patients with r/r B-ALL who lack other curative options. The successful regulatory approval and manufacturing process demonstrate feasibility for indigenous CAR T-cell therapies in low- and middle-income countries. Determination of the optimal dosing will guide future Phase 2 studies to further evaluate efficacy and safety.

Conclusion

This pioneering Phase I/Ib trial of Tali-cel™ establishes the feasibility and safety of an indigenously developed humanized CD19 CAR T-cell therapy in pediatric and young adult patients with r/r B-ALL, setting the stage for expanded clinical evaluation and broader accessibility.

References

  1. Novartis/2017 -- FDA Approval of Tisagenlecleucel (Kymriah®) for r/r B-ALL
  2. IIT Bombay & Tata Memorial Centre/2015-2024 -- Development and Clinical Trial of HCAR19 (Tali-cel™)
  3. Clinical Trial Registry of India (CTRI) -- CTRI/2021/05/033348 and CTRI/2023/03/050689

Original Source(s)

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

  • by 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

  • April 24, 2025

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