Actively Recruiting
Tris-CAR-T Cell Therapy for Recurrent Glioblastoma
Led by Beijing Tiantan Hospital · Updated on 2024-04-12
10
Participants Needed
1
Research Sites
474 weeks
Total Duration
On this page
Sponsors
B
Beijing Tiantan Hospital
Lead Sponsor
B
Beijing Neurosurgical Institute
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Tris-CAR-T Cell Therapy for Recurrent Glioblastoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 70 years old (inclusive)
- Diagnosed with recurrent glioblastoma and residual tumor after surgery at Beijing Tiantan Hospital
- Completed radiotherapy or drug treatments such as temozolomide or bevacizumab at least 4 weeks prior, with any side effects grade 1 or less (except hair loss or leukoplakia)
- Suitable for implantation of an Ommaya device confirmed by a physician
- Able to provide written informed consent
- Kanovsky Performance Status (KPS) of 70 or higher
- Life expectancy of at least 8 weeks as judged by researchers
- White blood cell count over 3.5 x 10^9/L within 14 days prior to PBMC collection
- Platelet count of at least 200 x 10^9/L within 14 days prior to PBMC collection
- Hemoglobin level of at least 120 g/L within 14 days prior to PBMC collection
- Total bilirubin of 20 µmol/L or less within 14 days prior to PBMC collection
- AST level of 2.5 times the upper limit of normal or less within 14 days prior to PBMC collection
- ALT level of 2.5 times the upper limit of normal or less within 14 days prior to PBMC collection
- Serum creatinine of 90 µmol/L or less within 14 days prior to PBMC collection
- Blood oxygen saturation of 95% or higher within 14 days prior to PBMC collection
- Negative for HIV antibody within 14 days prior to PBMC collection
- Fertile women must have a negative pregnancy test within 14 days prior to PBMC collection
- Patients of childbearing age agree to use contraception from screening until last infusion of Tris-CAR-T cells
You will not qualify if you...
- Kanovsky Performance Status (KPS) 70 or less
- History of severe allergies or highly allergic constitution
- Psychiatric or psychological disorders preventing cooperation with treatment and assessment
- Participation in other drug trials within 60 days before enrollment or receiving non-experimental glioblastoma treatments like stereotactic radiation or carmustine wafers
- Active infection or fever of unknown cause
- Serious or unstable diseases of heart, lung, liver, kidney, or blood systems including active hepatitis
- Autoimmune or immune system diseases such as rheumatoid arthritis, or known immunosuppressive conditions
- Neurological diseases like diffuse leptomeningeal disease or neurodegenerative disorders
- Known allergies to immunotherapy or related cellular products
- Previous gene therapy treatments
- Requirement for long-term immunosuppressant use
- History of organ transplantation or awaiting transplantation
- Pregnancy or breastfeeding
- Any other condition that investigators judge as unsuitable for the trial
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Beijing Tiantan Hospital
Beijing, Beijing Municipality, China, 100070
Actively Recruiting
Research Team
W
Wei Zhang, Prof.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here