Recurrent GlioblastomaPhase 1NCT02208362
Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
A Phase 1 study testing Arm 1: IL13Ra2-specific CAR Tcm cells, Arm 2: IL13Ra2-specific CAR Tcm cells and Arm 3: IL13Ra2-specific CAR Tcm cells in people with Recurrent Glioblastoma and Recurrent Malignant Glioma, run by City of Hope Medical Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. Read more about this study
- Who is it for?
- Ages 12 to 75 years
- Conditions the study is for
- Recurrent Glioblastoma, Recurrent Malignant Glioma, Recurrent WHO Grade II Glioma
- What is being tested?
- Arm 1: IL13Ra2-specific CAR Tcm cells, Arm 2: IL13Ra2-specific CAR Tcm cells and Arm 3: IL13Ra2-specific CAR Tcm cells
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2015to 10 May 2027
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- SCREENING INCLUSION CRITERIA
- Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG) after completing standard therapy
- Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial radiation therapy
- Karnofsky performance status (KPS) >= 60%
- Life expectancy > 4 weeks
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
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- City of Hope (COH) Clinical Pathology confirms IL13R alpha 2+ tumor expression by immunohistochemistry (>= 20%, 1+)
- All research participants must have the ability to understand and the willingness to sign a written informed consent
- ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION
- Research participant must not require more than 2 mg three times daily (TID) of dexamethasone on the day of PBMC collection.
- Research participant must have appropriate venous access
- At least 2 weeks must have elapsed since the research participant received his/her last dose of prior chemotherapy or radiation
- ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT
- Creatinine < 1.6 mg/dL
- White blood cell (WBC) > 2,000/dl or
- Absolute neutrophil count (ANC) > 1,000
- Platelets >= 100,000/dl
- International normalized ratio (INR) < 1.3
- Bilirubin < 1.5 mg/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limits of normal
- An interval of at least 12 weeks must have elapsed since the completion of initial radiation therapy
- Wash-out requirements (standard or investigational):
- At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen
- At least 23 days since the completion of Temodar and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment
- ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH CAR T CELL INFUSION
- Research participant has a released cryopreserved T cell product
- Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
- Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias
- Research participant does not have a fever exceeding 38.5° Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis
- Research participant serum total bilirubin does not exceed 2 x normal limit
- Research participant transaminases does not exceed 2 x normal limit
- Research participant serum creatinine =< 1.8 mg/dL
- Research participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell dose
- Research participant platelet count must be >= 100,000; however, if platelet level is between 75,000-99,000, then T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is >= 100,000
- Research participants must not require more than 2 mg TID of dexamethasone during T cell therapy
Who cannot join
- SCREENING EXCLUSION CRITERIA
- Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
- Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
- Research participant requires dialysis
- Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
- Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
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- Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
- Research participants with any other active malignancies
- Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
- Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
- Research participants who have confirmed human immunodeficiency virus (HIV) within 4 weeks of screening
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: Phase I Study of Cellular ImmunoTx Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Specific, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Pts With Rec/Ref MaligGlioma
This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. T cells are taken from the patient's blood and a modified gene is placed into them in the laboratory and this may help them recognize and kill glioma cells. Genetically modified T-cells may also help the body build an immune response against the tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous memory-enriched T cells (Arms 1, 2, 3, or 4 = Tcm or Arm 5 = Tn/mem) that are genetically modified using a self-inactivating (SIN) lentiviral vector to express an interleukin 13 receptor alpha 2 (IL13Ra2)-specific, hinge-optimized, 41BB-costimulatory chimeric antigen receptor (CAR), as well as a truncated CD19 (CD19t) for participants with recurrent/refractory malignant glioma in one of the following ways: (1) directly into the tumor (intratumoral), (2) into the tumor cavity (intracavitary), (3) into the lateral ventricles (intraventricular), or (4) into both the tumor/tumor cavity (intratumoral) and into the lateral ventricles (intraventricular) (dual delivery).
II. Determine maximum tolerated dose schedule (MTD)/maximum feasible dose schedule (MFD) and a recommended phase II dosing plan (RP2D) for each arm based on dose limiting toxicities (DLTs) and the full toxicity profile.
SECONDARY OBJECTIVES:
- In research participants who receive the full schedule of three CAR+ T cell doses:
- Estimate disease response rates,
- Estimate median overall survival, and
- Estimate the mean change from baseline in quality of life using the EORTC QLQ-C30 during and post treatment;
II. Describe cytokine levels (tumor cavity fluid, CSF, peripheral blood) over the study period.
III. Describe CAR T cell and endogenous immune populations (CSF, tumor cavity fluid, peripheral blood) over the study period; and IV. Identify tumor and tumor micro-environment markers associated with response to CAR T cells.
EXPLORATORY OBJECTIVES:
- Assess the timing and extent of brain inflammation following CAR T cell administration; II. Evaluate CAR T cell product characteristics; and
III. For research participants who undergo a second resection or autopsy:
- Evaluate CAR T cell persistence in the tumor micro-environment and the location of the CAR T cells with respect to the injection, and
- Evaluate IL13Rα2 antigen expression levels pre and post CAR T cell therapy.
OUTLINE: This is a dose-escalation study. Research subjects will receive an initial low dose (cycle 1) followed by 2 additional infusions at a higher cell dose (cycles 2 and 3) of autologous IL13Ra2-CAR/CD19t+ Tcm or Tn/mem, potentially followed by additional cycles at up to the highest tolerated cell dose (cycles 4+). CAR T cells will be administered in one of four ways:
ARM 1: (Intratumoral delivery a/f biopsy): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter. Patients who progress on intratumoral administration may move to intraventricular catheter for the optional infusions.
ARM 2: (Intratumoral delivery a/f biopsy/Intracavitary a/f resection): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter, or into the tumor resection cavity via intracavitary (ICTr) catheter. Patients who progress on intratumoral/intracavitary administration may move to intraventricular catheter for the optional infusions.
ARM 3: (Intraventricular delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via intraventricular (ICV) catheter.
ARM 4: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via ICTb/r catheter and ICV catheter. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).
ARM 5: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tn/mem via ICTb/r catheter and ICV catheter. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).
CAR T cells will be administered at one of three dose schedules:
- Dose Schedule 1: Cycle 1 - 2x106 CAR T cells, Cycle 2 \& 3 - 10x106 CAR T cells, Total dose - 22x106 CAR T cells; Optional cycles ≤10x106 CAR T cells
- Dose Schedule 2: Cycle 1 - 10x106 CAR T cells, Cycle 2 \& 3 - 50x106 CAR T cells, Total dose - 110x106 CAR T cells; Optional cycles ≤50x106 CAR T cells
- Dose Schedule 3: Cycle 1 - 20x106 CAR T cells, Cycle 2 \& 3 - 100x106 CAR T cells, Total dose - 220x106 CAR T cells; Optional cycles ≤100x106 CAR T cells
After completion of the study treatment, patients are followed up at 4 weeks, 3, 6, 8, 10, and 12 months, and then yearly for 15 years.
- Conditions
- Recurrent Glioblastoma, Recurrent Malignant Glioma, Recurrent WHO Grade II Glioma, Recurrent WHO Grade III Glioma, Refractory Glioblastoma, Refractory Malignant Glioma
- Being tested
- Arm 1: IL13Ra2-specific CAR Tcm cells, Arm 2: IL13Ra2-specific CAR Tcm cells, Arm 3: IL13Ra2-specific CAR Tcm cells, Arm 4: IL13Ra2-specific CAR Tcm cells, Arm 5: IL13Ra2-specific CAR Tn/mem cells
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1: IL13Ra2-specific CAR Tcm cellsBiological
Also called Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ Tcm
Given via intratumoral catheter
Arm 2: IL13Ra2-specific CAR Tcm cellsBiological
Also called Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ Tcm
Given via intratumoral/intracavitary catheter
Arm 3: IL13Ra2-specific CAR Tcm cellsBiological
Also called Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ Tcm
Given via intraventricular catheter
Arm 4: IL13Ra2-specific CAR Tcm cellsBiological
Also called Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ Tcm
Given via intratumoral or intracavitary, and via intraventricular catheter
Arm 5: IL13Ra2-specific CAR Tn/mem cellsBiological
Also called Autologous IL13(EQ)BBzeta/CD19t+ Tn/mem-enriched T Cells, IL13Ra2-CAR/CD19t+ Tn/mem
Given via intratumoral or intracavitary, and via intraventricular catheter
Laboratory Biomarker AnalysisOther
Correlative studies
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging, MRI
Correlative studies
Magnetic Resonance Spectroscopic ImagingProcedure or surgery
Also called 1H- Nuclear Magnetic Resonance Spectroscopic Imaging, 1H-nuclear magnetic resonance spectroscopic imaging, Magnetic Resonance Spectroscopy, MRS
Correlative studies
Quality-of-Life AssessmentOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]) | Experimental | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb] Receives: Biological: Arm 1: IL13Ra2-specific CAR Tcm cells; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Quality-of-Life Assessment |
| Arm 2 (Tcm-derived CAR T cells, ICTb/r) | Experimental | Arm 2 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb] or Intracavitary a/f resection [ICTr]) Receives: Biological: Arm 2: IL13Ra2-specific CAR Tcm cells; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Quality-of-Life Assessment |
| Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]) | Experimental | Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]) Receives: Biological: Arm 3: IL13Ra2-specific CAR Tcm cells; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Quality-of-Life Assessment |
| Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) | Experimental | Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) Receives: Biological: Arm 4: IL13Ra2-specific CAR Tcm cells; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Quality-of-Life Assessment |
| Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) | Experimental | Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) Receives: Biological: Arm 5: IL13Ra2-specific CAR Tn/mem cells; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade 3 or Higher Toxicity Related to CAR T Cells
Grade 3 or higher toxicity profile for adverse events probably or definitely related to CAR T cells as assessed by the NCI CTCAE version 4.0.
Measured: An average of 11 months
Number of Participants Experiencing a Dose Limiting Toxicity (DLT)
Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT is defined as events attributable to T-cell infusion (probable or definite) with a few expected events that resolve within a specified time and occurring from the time of initial CAR T cell infusion through 1 week following the last infusion cycle (not including optional cycles) unless otherwise specified in this definition:
- Two grade 3 toxicities at the same dose with the exception of those grade 3 toxicities listed below.
- Any grade 3 Cytokine release syndrome (CRS) toxicity lasting more than 72 hours without intervention
- Any grade 3 or higher allergic reaction
- Any grade 3 or higher autoimmune reaction
- Any grade 4 toxicity
Measured: Up to 1 week following the last course, up to a total of 4 weeks (not including optional courses 4-6)
Secondary outcomes (2)
Number of Participants With Active Response Determined by Response Assessment in Neuro-Oncology (RANO) Criteria
Counts of active response and progression determined by RANO. Participants achieving stable disease (SD), partial remission (PR), or complete remission (CR) are counted as active.
RANO:
Complete Response (CR): Disappearance of all enhancing disease sustained for 4 weeks, stable or improved FLAIR/T2 lesions, no new lesions, off corticosteroids and neurologically stable or improved.
Partial Response (PR): At least a 50% decrease of all measurable enhancing lesions sustained for 4 weeks, no progression of non-measurable disease, stable or improved FLAIR/T2 lesions, no new lesions, corticosteroids dose stable or reduced and neurologically stable or improved.
Stable Disease (SD): Does not qualify for CR, PR or PD, stable FLAIR/T2 lesions, stable or reduced corticosteroids, clinically stable Progressive Disease (PD): At least a 25% increase in enhancing lesions despite stable or increasing steroid dose, increase in FLAIR/T2 lesions, any new lesions, clinical deteriorations.
Measured: Between 4 and 8 weeks post 1st CAR T infusion
Number of Participants Alive at 6 Months
Participants were assessed for vital status up to 6 months post surgery.
Measured: From surgery to death from any cause or six months, whichever occurred first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2014 (estimated)
- Study start18 May 2015
- Primary completion8 Feb 2021
- Study completion10 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)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 City of Hope Medical CenterThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Behnam Badie, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02208362
- Sponsor's protocol ID
- 13384
- Other IDs
- NCI-2014-01488, 13384, P30CA033572, R01FD005129
- Status last verified
- Jul 2026
- First submitted
- 1 Aug 2014
- Last updated
- 28 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brown 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 38454126Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D'Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016 Dec 29;375(26):2561-9. doi: 10.1056/NEJMoa1610497.
PubMed 28029927
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Cellular ImmunoTx Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Specific, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Pts With Rec/Ref MaligGlioma
- ClinicalTrials.gov ID
- NCT02208362
- Acronym / sponsor ID
- 13384
- Conditions
- Recurrent Glioblastoma, Recurrent Malignant Glioma, Recurrent WHO Grade II Glioma, Recurrent WHO Grade III Glioma, Refractory Glioblastoma, Refractory Malignant Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 65 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Food and Drug Administration (FDA)
- Study start
- 18 May 2015 (actual)
- Primary completion
- 8 Feb 2021 (actual)
- Study completion
- 10 May 2027 (estimated)
- First posted
- 5 Aug 2014 (estimated)
- Results
- Posted 30 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. T cells are taken from the patient's blood and a modified gene is placed into them in the laboratory and this may help them recognize and kill glioma cells. Genetically modified T-cells may also help the body build an immune response against the tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous memory-enriched T cells (Arms 1, 2, 3, or 4 = Tcm or Arm 5 = Tn/mem) that are genetically modified using a self-inactivating (SIN) lentiviral vector to express an interleukin 13 receptor alpha 2 (IL13Ra2)-specific, hinge-optimized, 41BB-costimulatory chimeric antigen receptor (CAR), as well as a truncated CD19 (CD19t) for participants with recurrent/refractory malignant glioma in one of the following ways: (1) directly into the tumor (intratumoral), (2) into the tumor cavity (intracavitary), (3) into the lateral ventricles (intraventricular), or (4) into both the tumor/tumor cavity (intratumoral) and into the lateral ventricles (intraventricular) (dual delivery).
II. Determine maximum tolerated dose schedule (MTD)/maximum feasible dose schedule (MFD) and a recommended phase II dosing plan (RP2D) for each arm based on dose limiting toxicities (DLTs) and the full toxicity profile.
SECONDARY OBJECTIVES:
- In research participants who receive the full schedule of three CAR+ T cell doses:
- Estimate disease response rates,
- Estimate median overall survival, and
- Estimate the mean change from baseline in quality of life using the EORTC QLQ-C30 during and post treatment;
II. Describe cytokine levels (tumor cavity fluid, CSF, peripheral blood) over the study period.
III. Describe CAR T cell and endogenous immune populations (CSF, tumor cavity fluid, peripheral blood) over the study period; and IV. Identify tumor and tumor micro-environment markers associated with response to CAR T cells.
EXPLORATORY OBJECTIVES:
- Assess the timing and extent of brain inflammation following CAR T cell administration; II. Evaluate CAR T cell product characteristics; and
III. For research participants who undergo a second resection or autopsy:
- Evaluate CAR T cell persistence in the tumor micro-environment and the location of the CAR T cells with respect to the injection, and
- Evaluate IL13Rα2 antigen expression levels pre and post CAR T cell therapy.
OUTLINE: This is a dose-escalation study. Research subjects will receive an initial low dose (cycle 1) followed by 2 additional infusions at a higher cell dose (cycles 2 and 3) of autologous IL13Ra2-CAR/CD19t+ Tcm or Tn/mem, potentially followed by additional cycles at up to the highest tolerated cell dose (cycles 4+). CAR T cells will be administered in one of four ways:
ARM 1: (Intratumoral delivery a/f biopsy): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter. Patients who progress on intratumoral administration may move to intraventricular catheter for the optional infusions.
ARM 2: (Intratumoral delivery a/f biopsy/Intracavitary a/f resection): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter, or into the tumor resection cavity via intracavitary (ICTr) catheter. Patients who progress on intratumoral/intracavitary administration may move to intraventricular catheter for the optional infusions.
ARM 3: (Intraventricular delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via intraventricular (ICV) catheter.
ARM 4: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via ICTb/r catheter and ICV catheter. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).
ARM 5: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tn/mem via ICTb/r catheter and ICV catheter. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).
CAR T cells will be administered at one of three dose schedules:
- Dose Schedule 1: Cycle 1 - 2x106 CAR T cells, Cycle 2 \& 3 - 10x106 CAR T cells, Total dose - 22x106 CAR T cells; Optional cycles ≤10x106 CAR T cells
- Dose Schedule 2: Cycle 1 - 10x106 CAR T cells, Cycle 2 \& 3 - 50x106 CAR T cells, Total dose - 110x106 CAR T cells; Optional cycles ≤50x106 CAR T cells
- Dose Schedule 3: Cycle 1 - 20x106 CAR T cells, Cycle 2 \& 3 - 100x106 CAR T cells, Total dose - 220x106 CAR T cells; Optional cycles ≤100x106 CAR T cells
After completion of the study treatment, patients are followed up at 4 weeks, 3, 6, 8, 10, and 12 months, and then yearly for 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]) | Experimental | Biological: Arm 1: IL13Ra2-specific CAR Tcm cells, Other: Laboratory Biomarker Analysis, Procedure: Magnetic Resonance Imaging, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Quality-of-Life AssessmentArm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb] |
| Arm 2 (Tcm-derived CAR T cells, ICTb/r) | Experimental | Biological: Arm 2: IL13Ra2-specific CAR Tcm cells, Other: Laboratory Biomarker Analysis, Procedure: Magnetic Resonance Imaging, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Quality-of-Life AssessmentArm 2 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb] or Intracavitary a/f resection [ICTr]) |
| Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]) | Experimental | Biological: Arm 3: IL13Ra2-specific CAR Tcm cells, Other: Laboratory Biomarker Analysis, Procedure: Magnetic Resonance Imaging, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Quality-of-Life AssessmentArm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]) |
| Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) | Experimental | Biological: Arm 4: IL13Ra2-specific CAR Tcm cells, Other: Laboratory Biomarker Analysis, Procedure: Magnetic Resonance Imaging, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Quality-of-Life AssessmentArm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) | Experimental | Biological: Arm 5: IL13Ra2-specific CAR Tn/mem cells, Other: Laboratory Biomarker Analysis, Procedure: Magnetic Resonance Imaging, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Quality-of-Life AssessmentArm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
Who may qualify
- Ages
- 12 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (35 listed)
- SCREENING INCLUSION CRITERIA
- Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG) after completing standard therapy
- Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial radiation therapy
- Karnofsky performance status (KPS) >= 60%
- Life expectancy > 4 weeks
Key exclusion criteria (11 listed)
- SCREENING EXCLUSION CRITERIA
- Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
- Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
- Research participant requires dialysis
- Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
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 |
|---|---|---|
| Arm 1: IL13Ra2-specific CAR Tcm cellsAlso: Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ TcmGiven via intratumoral catheter | Biological | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]) |
| Arm 2: IL13Ra2-specific CAR Tcm cellsAlso: Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ TcmGiven via intratumoral/intracavitary catheter | Biological | Arm 2 (Tcm-derived CAR T cells, ICTb/r) |
| Arm 3: IL13Ra2-specific CAR Tcm cellsAlso: Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ TcmGiven via intraventricular catheter | Biological | Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]) |
| Arm 4: IL13Ra2-specific CAR Tcm cellsAlso: Autologous IL13(EQ)BBzeta/CD19t+ Tcm-enriched T Cells, IL13Ra2-CAR/CD19t+ TcmGiven via intratumoral or intracavitary, and via intraventricular catheter | Biological | Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Arm 5: IL13Ra2-specific CAR Tn/mem cellsAlso: Autologous IL13(EQ)BBzeta/CD19t+ Tn/mem-enriched T Cells, IL13Ra2-CAR/CD19t+ Tn/memGiven via intratumoral or intracavitary, and via intraventricular catheter | Biological | Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]), Arm 2 (Tcm-derived CAR T cells, ICTb/r), Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]), Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV), Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging, MRICorrelative studies | Procedure or surgery | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]), Arm 2 (Tcm-derived CAR T cells, ICTb/r), Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]), Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV), Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Magnetic Resonance Spectroscopic ImagingAlso: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging, 1H-nuclear magnetic resonance spectroscopic imaging, Magnetic Resonance Spectroscopy, MRSCorrelative studies | Procedure or surgery | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]), Arm 2 (Tcm-derived CAR T cells, ICTb/r), Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]), Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV), Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
| Quality-of-Life AssessmentAncillary studies | Other | Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb]), Arm 2 (Tcm-derived CAR T cells, ICTb/r), Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV]), Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV), Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV) |
Primary outcome
Number of Participants With Grade 3 or Higher Toxicity Related to CAR T Cells
Time frame: An average of 11 months
Grade 3 or higher toxicity profile for adverse events probably or definitely related to CAR T cells as assessed by the NCI CTCAE version 4.0.
Number of Participants Experiencing a Dose Limiting Toxicity (DLT)
Time frame: Up to 1 week following the last course, up to a total of 4 weeks (not including optional courses 4-6)
Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT is defined as events attributable to T-cell infusion (probable or definite) with a few expected events that resolve within a specified time and occurring from the time of initial CAR T cell infusion through 1 week following the last infusion cycle (not including optional cycles) unless otherwise specified in this definition: 1. Two grade 3 toxicities at the same dose with the exception of those grade 3 toxicities listed below. 2. Any grade 3 Cytokine release syndrome (CRS) toxicity lasting more than 72 hours without intervention 3. Any grade 3 or higher allergic reaction 4. Any grade 3 or higher autoimmune reaction 5. Any grade 4 toxicity
2 secondary outcomes
Number of Participants With Active Response Determined by Response Assessment in Neuro-Oncology (RANO) Criteria
Time frame: Between 4 and 8 weeks post 1st CAR T infusion
Number of Participants Alive at 6 Months
Time frame: From surgery to death from any cause or six months, whichever occurred first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: 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.
- Derived from this study: PubMed 28029927Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D'Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016 Dec 29;375(26):2561-9. doi: 10.1056/NEJMoa1610497.
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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. This study is not recruiting at the moment.
Behnam Badie principal investigator
City of Hope Medical Center
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 Arm 1: IL13Ra2-specific CAR Tcm cells, Arm 2: IL13Ra2-specific CAR Tcm cells and Arm 3: IL13Ra2-specific CAR Tcm cells in people with Recurrent Glioblastoma and Recurrent Malignant Glioma, run by City of Hope Medical Center at 1 site in United States.
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 35 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 28 Jul 2026. 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 United States. 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?
Yes. Results are posted in the registry (first posted 30 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade 3 or Higher Toxicity Related to CAR T Cells (time frame: An average of 11 months). The study lists 2 primary outcomes in all. 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 NCT02208362, which also lists 2 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 28 Jul 2026.