NCT05577091

Tris-CAR-T Cell Therapy for Recurrent Glioblastoma

Recruiting now Phase 1 Last updated 12 April 2024

What this trial tests

Phase 1 trial testing Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes. in Recurrent Glioblastoma in 10 participants. Currently enrolling.

Timeline

30 September 2023

Primary endpoint
1 November 2024

1 November 2032

Quick facts

Lead sponsor	Beijing Tiantan Hospital
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	30 September 2023
Primary completion	1 November 2024
Estimated completion	1 November 2032
Sites	1 location across China

Drugs / interventions tested

• Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.

Conditions studied

• Recurrent Glioblastoma — all drugs for Recurrent Glioblastoma →

Sponsor

Beijing Tiantan Hospital

Who can join

Adults 18 to 70, any sex, with Recurrent Glioblastoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase 1 study of recurrent glioblastoma locoregional adoptive therapy with autologous peripheral blood T cells lentivirally transduced to express a dual-target, truncated IL7Ra modified chimeric antigen receptor (CAR), delivered by Ommaya reservoir, a pre-indwelled catheter in the tumor resection cavity or ventricle. Patients with pathological confirmation of glioblastoma and radiological evidence of recurrence are candidates for this clinical trial. If the patient meets all other eligibility criteria, and meets none of the exclusion criteria, will have leukapheresis, and a subsequent Ommaya reservoir implantation. T cells will be isolated from the PBMC sample and then be bioengineered into a 4th generation CAR-T cell, Tris-CAR-T cells.

Recipients will be assigned to three courses in the order of enrollment. The first 2 patients will be assigned to the low-dose group. The second 2 patients will be assigned to the high dose group. The first 4 patients will have at least one dose of autologous Tris-CAR-T cells delivery via the Ommaya reservoir, at a maximum of 6 doses. The interval between the first and the second dose is 28 days, and the rest doses will be administered weekly. The last 6 patients will be assigned to the consecutive multidose group, and will receive a weekly dose of autologous Tris-CAR-T cells for a maximum of 8 weeks. All patients will undergo studies including MRI to evaluate the effect of the CAR-T cells, physical examination, and cerebrospinal fluid cytokine assays to evaluate side effects. All patients will undergo a long-term follow-up.

The hypothesis is that an adequate amount of Tris-CAR-T cells can be manufactured to complete all the three courses. The other hypothesis is that Tris-CAR-T cells can safely and effectively be administered through the Ommaya reservoir to allow the CAR-T cells to directly interact with the tumor cells for each patient enrolled in the study. The primary aim of the study will be to evaluate the safety of Tris-CAR-T administration. Secondary aims of the study will include evaluating CAR-T cell distribution within cerebrospinal fluid and peripheral blood, tumor progress post-CAR-T cell infusion, and, if tissue samples from multiple time points are available, also evaluate the degree of target expression, biological characteristics of samples at diagnosis versus at recurrence or progression.

Publications & conference data

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

1. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
   Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
2. CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.
   Luksik AS, Yazigi E, Shah P, Jackson CM. · · 2023 · cited 60× · PMID 36900205 · DOI 10.3390/cancers15051414
3. Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape.
   Zhai Y, Du Y, Li G, Yu M, et al · · 2023 · cited 46× · PMID 38143263 · DOI 10.1038/s41392-023-01708-w
4. CAR-T cell therapy for the treatment of adult high-grade gliomas.
   Park S, Maus MV, Choi BD. · · 2024 · cited 38× · PMID 39702579 · DOI 10.1038/s41698-024-00753-0
5. Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives.
   Salvato I, Marchini A. · · 2024 · cited 32× · PMID 38610954 · DOI 10.3390/cancers16071276
6. Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.
   Chang C, Chavarro VS, Gerstl JVE, Blitz SE, et al · · 2024 · cited 29× · PMID 38928445 · DOI 10.3390/ijms25126733
7. CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies.
   Agosti E, Garaba A, Antonietti S, Ius T, et al · · 2024 · cited 21× · PMID 39000281 · DOI 10.3390/ijms25137174
8. Therapeutic approaches to modulate the immune microenvironment in gliomas.
   Sarantopoulos A, Ene C, Aquilanti E. · · 2024 · cited 19× · PMID 39443641 · DOI 10.1038/s41698-024-00717-4