NCT04557436: PBLTT52CAR19

TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL)

Completed Phase 1 Last updated 7 March 2024

What this trial tests

Phase 1 trial testing PBLTT52CAR19 in B Acute Lymphoblastic Leukemia in 9 participants. Completed in 5 March 2024.

Timeline

12 August 2020

Primary endpoint
5 March 2024

5 March 2024

Quick facts

Lead sponsor	Great Ormond Street Hospital for Children NHS Foundation Trust
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	9
Start date	12 August 2020
Primary completion	5 March 2024
Estimated completion	5 March 2024
Sites	1 location across United Kingdom

Drugs / interventions tested

• PBLTT52CAR19 — full drug profile →

Conditions studied

• B Acute Lymphoblastic Leukemia — all drugs for B Acute Lymphoblastic Leukemia →

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Who can join

Adults 6 Months to 18, any sex, with B Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCRαβ-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. They have been transduced to express and anti-CD19 chimeric antigen receptor (CAR19) using a lentiviral vector that also incorporates CRISPR guides for genome editing of CD52 and TRAC loci in the presence of transiently provided Cas9.

Recognition by TT52CAR19 T cells mediates eradication of CD19+ leukaemia and other CD19+ B cells through T cell mediated cytotoxicity.

This study aims to apply PBLTT52CAR19 T cells to secure molecular remission in children with relapsed/refractory B-ALL ahead of programmed allogeneic stem cell transplantation. The cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current applications and future perspective of CRISPR/Cas9 gene editing in cancer.
   Wang SW, Gao C, Zheng YM, Yi L, et al · · 2022 · cited 305× · PMID 35189910 · DOI 10.1186/s12943-022-01518-8
2. Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia.
   Ottaviano G, Georgiadis C, Gkazi SA, Syed F, et al · · 2022 · cited 141× · PMID 36288281 · DOI 10.1126/scitranslmed.abq3010
3. Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy.
   Liu Z, Shi M, Ren Y, Xu H, et al · · 2023 · cited 93× · PMID 36797756 · DOI 10.1186/s12943-023-01738-6
4. Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.
   Lei T, Wang Y, Zhang Y, Yang Y, et al · · 2024 · cited 68× · PMID 39455854 · DOI 10.1038/s41375-024-02444-y
5. CRISPR/Cas9 systems: Delivery technologies and biomedical applications.
   Du Y, Liu Y, Hu J, Peng X, et al · · 2023 · cited 62× · PMID 38089835 · DOI 10.1016/j.ajps.2023.100854
6. CRISPR/Cas9 Delivery System Engineering for Genome Editing in Therapeutic Applications.
   Cheng H, Zhang F, Ding Y. · · 2021 · cited 59× · PMID 34683943 · DOI 10.3390/pharmaceutics13101649
7. Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy.
   Ahmadi SE, Soleymani M, Shahriyary F, Amirzargar MR, et al · · 2023 · cited 55× · PMID 36854897 · DOI 10.1038/s41417-023-00597-z
8. Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology.
   Tao R, Han X, Bai X, Yu J, et al · · 2024 · cited 51× · PMID 38449862 · DOI 10.3389/fimmu.2024.1354825