Recurrent GlioblastomaPhase 1NCT05577091
Tris-CAR-T Cell Therapy for Recurrent Glioblastoma
A Phase 1 study testing Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes. in people with Recurrent Glioblastoma, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Recurrent Glioblastoma
- What is being tested?
- Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2023to 1 Nov 2032
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 years to 70 years (including cut-off values).
- Patients with history of glioblastoma are diagnosed with recurrent glioblastoma and residual tumor after intracranial tumor resection/biopsy performed in Beijing Tiantan Hospital.
- Patients who finished radiotherapy or temozolomide/bevacizumab or other drugs for at least 4 weeks. All toxicities of prior treatment should be defined as less than or equal to grade 1 (except for toxicities such as hair loss or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 5.0).
- Patients who is suitable for craniotocerebrospinal fluid shunt and attachment (Ommaya device) implantation confirmed by a competent physician.
- Patients and/or legal representative is able to sign written informed consent.
- Kanovsky Performance Status (KPS) ≥ 70.
Show all 18Show fewer
- According to the researchers' judgment, the life expectancy ≥ 8 weeks.
- White blood cells (WBC) > 3.50×10^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Platelet ≥ 200×10^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Hemoglobin ≥ 120 g/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Total bilirubin ≤ 20 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Aspartic acid aminotransferase (AST) ≤ 2.5×42 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Alanine aminotransferase (ALT) ≤ 2.5×41 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Serum creatinine ≤ 90 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
- Blood oxygen saturation ≥ 95% (performed within 14 days prior to PBMC collection unless otherwise noted).
- Seronegative of the combination of human immunodeficiency virus (HIV) antibody (Ab) (performed within 14 days prior to PBMC collection unless otherwise noted).
- Fertile women: a negative serum pregnancy test (performed within 14 days prior to PBMC collection unless otherwise noted).
- The patient agrees that contraception should be used in patients of childbearing age for at least 3 months from screening to the last infusion of Tris-CAR-T cells. The period of childbearing age is defined as unsurgically neutered (men and women) or without menopause for more than 1 year (women only).
Who cannot join
- Kanovsky Performance Status (KPS) ≤ 70.
- Highly allergic constitution or severe allergies history.
- Those who have psychiatric or psychological diseases and cannot cooperate with treatment and efficacy assessment.
- Receive other drug trials within 60 days before enrollment, or receive other routine treatment in non-experimental designs for glioblastoma, such as stereotactic radiation therapy or placement of carmustine wafers.
- Combined with infection, active infection, fever of unknown cause.
- Combined with serious or unstable heart, lung, liver, kidney and hematopoietic system diseases, including active hepatitis.
Show all 14Show fewer
- Combined with inflammation and immune system diseases (such as rheumatoid arthritis), or known immunosuppressive diseases.
- Combined with neurological diseases, such as diffuse leptomeningeal disease, or neurodegenerative diseases.
- Known allergies to immunotherapy and related cellular products.
- Patients who have received any gene therapy before.
- Long-term use of immunosuppressants is required for any reason.
- Patients with a history of organ transplantation or who are waiting for organ transplantation.
- Special cases: pregnancy or lactation.
- Other circumstances in which the investigators believe the patient is unsuitable for this trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital
Beijing, Beijing Municipality, 100070
Wei Zhang, Prof., +8618010212661, zhangwei02@bjtth.org
You Zhai, Dr.
About this study
Official title: Phase 1 Study of Autologous Tris-CAR-T Cell Locoregional Immunotherapy for Recurrent Glioblastoma
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.
Read the detailed description
The autologous Tris-CAR-T cell, targeting both CD44 and CD133, the two inverse correlated targets, introduced truncated IL7Ra to the intracellular domain of the CAR molecule, and has shown ideal survival and tumor suppression in our previous studies. The cells will be tested for safety and kinetics in this clinical trial.
All patients are required to have an Ommaya reservoir in the tumor resection cavity before CAR-T cell infusion. Ommaya reservoir placement is done by surgery.
Autologous Tris-CAR-T cells will be manufactured via CliniMACS Instrument (Miltenyi Biotec). Cells will be thawed and sterily filled to infuse the patients. Each infusion will take between 5 and 10 minutes. We will then monitor the patient in the hospital for at least 3 days after the first dose of infusion. If the first infusion is tolerated well and the patient is assigned for multidose treatment, a second infusion may be given 28 days after the initial infusion for the first 4 patients (adverse effect assessment), and 7 days for the last 6 patients. Patients will be monitored in the hospital for no longer than 1 day. And the subsequent infusion will be done in the same manner. The treatment will be proceeded in the Department of Neurosurgery, Beijing Tiantan Hospital. Patients who receive multidose treatment will need to stay in Beijing for up to 8 weeks from the first infusion so we can monitor for side effects and will be readmitted to the hospital if patient develops a fever. If patient develops severe fevers after discharge from the hospital, the patient will be readmitted to the hospital for close monitoring for at least one night for safety observation and adverse effects management.
The first 4 patients will have follow-up visits at weeks 2, 3, and 4, then at months 3, 6, and 9 post-infusion. Patients of the consecutive multidose group will have follow-up visits at week 2, then at months 1 and 3 post-infusion. All patients receive long-term twice a year for a total of 15 years.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests:
- Physical exam
- Blood routine, serum biochemical test, kidney and liver function
- Measurements of the tumor by routine MRI
Medical tests during and after treatment--
The patient will receive standard medical tests when they are getting the infusions and afterward:
- Physical exams
- Blood routine, serum biochemical test, kidney and liver function, serum and (or) cerebrospinal fluid analysis
- Measurements of the tumor by MRI. Cerebrospinal fluid may be drawn from the patient's existing Ommaya reservoir preferentially, or via lumbar puncture before each infusion and at each time of follow-up. This procedure can be done at the bedside under local anesthesia and about 1ml of cerebrospinal fluid will be removed. Additional cerebrospinal fluid may be removed when intracranial hypertension occurs or other clinical needs.
To learn more about the pharmacokinetics of autologous Tris-CAR-T cells, peripheral blood will be obtained simultaneously with the cerebrospinal fluid collection. The amount of blood taken will be based on clinical need, for approximately 5 mL each time.
If the tumor samples of the patients are obtained, we will request a sample to be used for research purposes.
The patient will receive supportive care for any acute or chronic cytotoxicity, including blood components, cytokine antagonists, glucocorticoids, antibiotics, and other interventions as appropriate.
- Conditions
- Recurrent Glioblastoma
- Being tested
- Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.
- Keywords
- Recurrent Glioblastoma, Immunotherapy, Adverse Events
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.Genetic
Also called Autologous Tris-CAR-T cell.
Intratumoral or intraventricular administration via Ommaya reservoir.
Dose level 0: 1×10^7 autologous Tris-CAR-T cells, at least one dose, maximum 6 doses, 2 patients.
Dose level 1: 1×10^8/ 5×10^6 autologous Tris-CAR-T cells, at least one dose, maximum 6 doses, 2 patients. The dose of Dose level 1 will refer to the adverse effect of Dose level 0. When dose-related side effects occurred in 2 patients in the Dose level 0, the dose should be reduced to 5×10^6 cells.
In Dose levels 0 and 1, the second dose will be infused 28 days after the first dose, and the subsequent doses will be administered weekly.
Dose level 2: 5×10^7 autologous Tris-CAR-T cells, weekly administered, maximum 8 weeks, 4 patients. If the results of Dose levels 0 and 1 suggested that dose-related toxic side effects could have occurred in the 1×10^7cells dose, the researcher would re-determine the dosage of the multidose clinical exploration study.
| Study group | Role | What they receive |
|---|---|---|
| Autologous Tris-CAR-T cell | Experimental | Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity. Receives: Genetic: Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: any adverse events associated with one or multiple autologous Tris-CAR-T cell infusions will be assessed by CTCAE v5.0.
Assesing the type, frequency, severity, and duration of adverse events as a result of autologous Tris-CAR-T cell infusion via physical, laboratory and imaging examination.
Measured: 6 months
Secondary outcomes (3)
CAR-T pharmacokinetics: the distribution, persistence of autologous Tris-CAR-T cell in the cerebrospinal fluid (CSF) and peripheral blood will be measured by qPCR.
The trafficking of autologous Tris-CAR-T cell in the CSF and peripheral blood will be assessed by quantifying the mRNA of CAR gene at the time of each infusion as well as at each time of follow-up via CSF extraction/ lumbar puncture and blood collection. CSF and peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Measured: 6 months
CAR-T pharmacodynamics: chemokines and cytokines produced by autologous Tris-CAR-T cell in the cerebrospinal fluid (CSF) and peripheral blood will be measured by Olink Proteomics.
The effect and its persistence of autologous Tris-CAR-T cell in the CSF and peripheral blood will be assessed via investigating the concentration of chemokines and cytokines. CSF and peripheral blood samples will be harvested at the time of each infusion as well as at each time of follow-up via CSF extraction/ lumbar puncture and blood collection. IL-6, TNF-α, IFN-γ, CCL2, CXCL10, G-CSF, GM-CSF, IL-10, IL-15, IL-7 and IL-1α will be investigated. CSF and peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Measured: 6 months
CAR-T therapeutic effect evaluation: the therapeutic effect of autologous Tris-CAR-T cell will be assessed by iRANO.
The total lesions will be mesured by MRI. Total lesions will be collected and calcultated prior to the initial infusion and will be set as baseline.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start30 Sep 2023
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Recipients with the Ommaya reservoir implanted will be assigned to three courses. Arm A: Two patients, 1×10\^7 autologous Tris-CAR-T, at least 1 dose, maximum 6 doses. Arm B: Two patients 1×10\^8 autologous Tris-CAR-T, at least 1 dose, maximum 6 doses. Arm C: Six patients 5×10\^7 autologous Tris-CAR-T, maximum 8 doses.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Neurosurgical Institute, Tasly Pharmaceutical Group Co., Ltd
- Responsible party
- Principal investigator, Wei Zhang, Beijing Tiantan Hospital
- Investigators
- Tao Jiang, Prof., Study chair, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05577091
- Sponsor's protocol ID
- TTSW2021-01
- Status last verified
- Apr 2024
- First submitted
- 1 Oct 2022
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bagley SJ, Logun M, Fraietta JA, Wang X, Desai AS, Bagley LJ, Nabavizadeh A, Jarocha D, Martins R, Maloney E, Lledo L, Stein C, Marshall A, Leskowitz R, Jadlowsky JK, Christensen S, Oner BS, Plesa G, Brennan A, Gonzalez V, Chen F, Sun Y, Gladney W, Barrett D, Nasrallah MP, Hwang WT, Ming GL, Song H, Siegel DL, June CH, Hexner EO, Binder ZA, O'Rourke DM. Intrathecal bivalent CAR T cells targeting EGFR and IL13Ralpha2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. 2024 May;30(5):1320-1329. doi: 10.1038/s41591-024-02893-z. Epub 2024 Mar 13.
PubMed 38480922Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW, Balaj L, Nikiforow S, Carter BS, Curry WT, Gallagher K, Maus MV. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med. 2024 Apr 11;390(14):1290-1298. doi: 10.1056/NEJMoa2314390. Epub 2024 Mar 13.
PubMed 38477966Brown CE, Hibbard JC, Alizadeh D, Blanchard MS, Natri HM, Wang D, Ostberg JR, Aguilar B, Wagner JR, Paul JA, Starr R, Wong RA, Chen W, Shulkin N, Aftabizadeh M, Filippov A, Chaudhry A, Ressler JA, Kilpatrick J, Myers-McNamara P, Chen M, Wang LD, Rockne RC, Georges J, Portnow J, Barish ME, D'Apuzzo M, Banovich NE, Forman SJ, Badie B. Locoregional delivery of IL-13Ralpha2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med. 2024 Apr;30(4):1001-1012. doi: 10.1038/s41591-024-02875-1. Epub 2024 Mar 7.
PubMed 38454126Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H, Schultz LM, Richards RM, Jiang L, Barsan V, Mancusi R, Geraghty AC, Good Z, Mochizuki AY, Gillespie SM, Toland AMS, Mahdi J, Reschke A, Nie EH, Chau IJ, Rotiroti MC, Mount CW, Baggott C, Mavroukakis S, Egeler E, Moon J, Erickson C, Green S, Kunicki M, Fujimoto M, Ehlinger Z, Reynolds W, Kurra S, Warren KE, Prabhu S, Vogel H, Rasmussen L, Cornell TT, Partap S, Fisher PG, Campen CJ, Filbin MG, Grant G, Sahaf B, Davis KL, Feldman SA, Mackall CL, Monje M. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature. 2022 Mar;603(7903):934-941. doi: 10.1038/s41586-022-04489-4. Epub 2022 Feb 7.
PubMed 35130560Vitanza NA, Johnson AJ, Wilson AL, Brown C, Yokoyama JK, Kunkele A, Chang CA, Rawlings-Rhea S, Huang W, Seidel K, Albert CM, Pinto N, Gust J, Finn LS, Ojemann JG, Wright J, Orentas RJ, Baldwin M, Gardner RA, Jensen MC, Park JR. Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis. Nat Med. 2021 Sep;27(9):1544-1552. doi: 10.1038/s41591-021-01404-8. Epub 2021 Jul 12.
PubMed 34253928
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Autologous Tris-CAR-T Cell Locoregional Immunotherapy for Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT05577091
- Acronym / sponsor ID
- TTSW2021-01
- Conditions
- Recurrent Glioblastoma
- Keywords
- Recurrent Glioblastoma, Immunotherapy, Adverse Events
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- Beijing Neurosurgical Institute, Tasly Pharmaceutical Group Co., Ltd
- Study start
- 30 Sep 2023 (actual)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Nov 2032 (estimated)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The autologous Tris-CAR-T cell, targeting both CD44 and CD133, the two inverse correlated targets, introduced truncated IL7Ra to the intracellular domain of the CAR molecule, and has shown ideal survival and tumor suppression in our previous studies. The cells will be tested for safety and kinetics in this clinical trial.
All patients are required to have an Ommaya reservoir in the tumor resection cavity before CAR-T cell infusion. Ommaya reservoir placement is done by surgery.
Autologous Tris-CAR-T cells will be manufactured via CliniMACS Instrument (Miltenyi Biotec). Cells will be thawed and sterily filled to infuse the patients. Each infusion will take between 5 and 10 minutes. We will then monitor the patient in the hospital for at least 3 days after the first dose of infusion. If the first infusion is tolerated well and the patient is assigned for multidose treatment, a second infusion may be given 28 days after the initial infusion for the first 4 patients (adverse effect assessment), and 7 days for the last 6 patients. Patients will be monitored in the hospital for no longer than 1 day. And the subsequent infusion will be done in the same manner. The treatment will be proceeded in the Department of Neurosurgery, Beijing Tiantan Hospital. Patients who receive multidose treatment will need to stay in Beijing for up to 8 weeks from the first infusion so we can monitor for side effects and will be readmitted to the hospital if patient develops a fever. If patient develops severe fevers after discharge from the hospital, the patient will be readmitted to the hospital for close monitoring for at least one night for safety observation and adverse effects management.
The first 4 patients will have follow-up visits at weeks 2, 3, and 4, then at months 3, 6, and 9 post-infusion. Patients of the consecutive multidose group will have follow-up visits at week 2, then at months 1 and 3 post-infusion. All patients receive long-term twice a year for a total of 15 years.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests:
- Physical exam
- Blood routine, serum biochemical test, kidney and liver function
- Measurements of the tumor by routine MRI
Medical tests during and after treatment--
The patient will receive standard medical tests when they are getting the infusions and afterward:
- Physical exams
- Blood routine, serum biochemical test, kidney and liver function, serum and (or) cerebrospinal fluid analysis
- Measurements of the tumor by MRI. Cerebrospinal fluid may be drawn from the patient's existing Ommaya reservoir preferentially, or via lumbar puncture before each infusion and at each time of follow-up. This procedure can be done at the bedside under local anesthesia and about 1ml of cerebrospinal fluid will be removed. Additional cerebrospinal fluid may be removed when intracranial hypertension occurs or other clinical needs.
To learn more about the pharmacokinetics of autologous Tris-CAR-T cells, peripheral blood will be obtained simultaneously with the cerebrospinal fluid collection. The amount of blood taken will be based on clinical need, for approximately 5 mL each time.
If the tumor samples of the patients are obtained, we will request a sample to be used for research purposes.
The patient will receive supportive care for any acute or chronic cytotoxicity, including blood components, cytokine antagonists, glucocorticoids, antibiotics, and other interventions as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Recipients with the Ommaya reservoir implanted will be assigned to three courses. Arm A: Two patients, 1×10^7 autologous Tris-CAR-T, at least 1 dose, maximum 6 doses. Arm B: Two patients 1×10^8 autologous Tris-CAR-T, at least 1 dose, maximum 6 doses. Arm C: Six patients 5×10^7 autologous Tris-CAR-T, maximum 8 doses.
| Arm | Type | Receives |
|---|---|---|
| Autologous Tris-CAR-T cell | Experimental | Genetic: Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age: 18 years to 70 years (including cut-off values).
- Patients with history of glioblastoma are diagnosed with recurrent glioblastoma and residual tumor after intracranial tumor resection/biopsy performed in Beijing Tiantan Hospital.
- Patients who finished radiotherapy or temozolomide/bevacizumab or other drugs for at least 4 weeks. All toxicities of prior treatment should be defined as less than or equal to grade 1 (except for toxicities such as hair loss or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 5.0).
- Patients who is suitable for craniotocerebrospinal fluid shunt and attachment (Ommaya device) implantation confirmed by a competent physician.
- Patients and/or legal representative is able to sign written informed consent.
Key exclusion criteria (14 listed)
- Kanovsky Performance Status (KPS) ≤ 70.
- Highly allergic constitution or severe allergies history.
- Those who have psychiatric or psychological diseases and cannot cooperate with treatment and efficacy assessment.
- Receive other drug trials within 60 days before enrollment, or receive other routine treatment in non-experimental designs for glioblastoma, such as stereotactic radiation therapy or placement of carmustine wafers.
- Combined with infection, active infection, fever of unknown cause.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.Also: Autologous Tris-CAR-T cell.Intratumoral or intraventricular administration via Ommaya reservoir. Dose level 0: 1×10^7 autologous Tris-CAR-T cells, at least one dose, maximum 6 doses, 2 patients. Dose level 1: 1×10^8/ 5×10^6 autologous Tris-CAR-T cells, at least one dose, maximum 6 doses, 2 patients. The dose of Dose level 1 will refer to the adverse effect of Dose level 0. When dose-related side effects occurred in 2 patients in the Dose level 0, the dose should be reduced to 5×10^6 cells. In Dose levels 0 and 1, the second dose will be infused 28 days after the first dose, and the subsequent doses will be administered weekly. Dose level 2: 5×10^7 autologous Tris-CAR-T cells, weekly administered, maximum 8 weeks, 4 patients. If the results of Dose levels 0 and 1 suggested that dose-related toxic side effects could have occurred in the 1×10^7cells dose, the researcher would re-determine the dosage of the multidose clinical exploration study. | Genetic | Autologous Tris-CAR-T cell |
Primary outcome
Safety: any adverse events associated with one or multiple autologous Tris-CAR-T cell infusions will be assessed by CTCAE v5.0.
Time frame: 6 months
Assesing the type, frequency, severity, and duration of adverse events as a result of autologous Tris-CAR-T cell infusion via physical, laboratory and imaging examination.
3 secondary outcomes
CAR-T pharmacokinetics: the distribution, persistence of autologous Tris-CAR-T cell in the cerebrospinal fluid (CSF) and peripheral blood will be measured by qPCR.
Time frame: 6 months
CAR-T pharmacodynamics: chemokines and cytokines produced by autologous Tris-CAR-T cell in the cerebrospinal fluid (CSF) and peripheral blood will be measured by Olink Proteomics.
Time frame: 6 months
CAR-T therapeutic effect evaluation: the therapeutic effect of autologous Tris-CAR-T cell will be assessed by iRANO.
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Background: PubMed 38480922Bagley SJ, Logun M, Fraietta JA, Wang X, Desai AS, Bagley LJ, Nabavizadeh A, Jarocha D, Martins R, Maloney E, Lledo L, Stein C, Marshall A, Leskowitz R, Jadlowsky JK, Christensen S, Oner BS, Plesa G, Brennan A, Gonzalez V, Chen F, Sun Y, Gladney W, Barrett D, Nasrallah MP, Hwang WT, Ming GL, Song H, Siegel DL, June CH, Hexner EO, Binder ZA, O'Rourke DM. Intrathecal bivalent CAR T cells targeting EGFR and IL13Ralpha2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. 2024 May;30(5):1320-1329. doi: 10.1038/s41591-024-02893-z. Epub 2024 Mar 13.
- Background: PubMed 38477966Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW, Balaj L, Nikiforow S, Carter BS, Curry WT, Gallagher K, Maus MV. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med. 2024 Apr 11;390(14):1290-1298. doi: 10.1056/NEJMoa2314390. Epub 2024 Mar 13.
- Background: PubMed 38454126Brown CE, Hibbard JC, Alizadeh D, Blanchard MS, Natri HM, Wang D, Ostberg JR, Aguilar B, Wagner JR, Paul JA, Starr R, Wong RA, Chen W, Shulkin N, Aftabizadeh M, Filippov A, Chaudhry A, Ressler JA, Kilpatrick J, Myers-McNamara P, Chen M, Wang LD, Rockne RC, Georges J, Portnow J, Barish ME, D'Apuzzo M, Banovich NE, Forman SJ, Badie B. Locoregional delivery of IL-13Ralpha2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med. 2024 Apr;30(4):1001-1012. doi: 10.1038/s41591-024-02875-1. Epub 2024 Mar 7.
- Background: PubMed 35130560Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H, Schultz LM, Richards RM, Jiang L, Barsan V, Mancusi R, Geraghty AC, Good Z, Mochizuki AY, Gillespie SM, Toland AMS, Mahdi J, Reschke A, Nie EH, Chau IJ, Rotiroti MC, Mount CW, Baggott C, Mavroukakis S, Egeler E, Moon J, Erickson C, Green S, Kunicki M, Fujimoto M, Ehlinger Z, Reynolds W, Kurra S, Warren KE, Prabhu S, Vogel H, Rasmussen L, Cornell TT, Partap S, Fisher PG, Campen CJ, Filbin MG, Grant G, Sahaf B, Davis KL, Feldman SA, Mackall CL, Monje M. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature. 2022 Mar;603(7903):934-941. doi: 10.1038/s41586-022-04489-4. Epub 2022 Feb 7.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tao Jiang, Prof. study chair
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Inverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes. in people with Recurrent Glioblastoma, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Zhang, Prof. (+861059976686, zhangwei02@bjtth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: any adverse events associated with one or multiple autologous Tris-CAR-T cell infusions will be assessed by CTCAE v5.0. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05577091, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.