Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
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
4 other identifiers
interventional
65
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 1, 2014
CompletedFirst Posted
Study publicly available on registry
August 5, 2014
CompletedStudy Start
First participant enrolled
May 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 8, 2021
CompletedResults Posted
Study results publicly available
October 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 8, 2026
ExpectedSeptember 3, 2025
August 1, 2025
5.7 years
August 1, 2014
December 15, 2023
August 18, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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: 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
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
Between 4 and 8 weeks post 1st CAR T infusion
Number of Participants Alive at 6 Months
From surgery to death from any cause or six months, whichever occurred first
Study Arms (5)
Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb])
EXPERIMENTALArm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy \[ICTb\]
Arm 2 (Tcm-derived CAR T cells, ICTb/r)
EXPERIMENTALArm 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])
EXPERIMENTALArm 3 (Tcm-derived CAR T cells, Intraventricular \[ICV\])
Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)
EXPERIMENTALArm 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)
EXPERIMENTALArm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)
Interventions
Given via intratumoral catheter
Given via intratumoral/intracavitary catheter
Given via intraventricular catheter
Given via intratumoral or intracavitary, and via intraventricular catheter
Given via intratumoral or intracavitary, and via intraventricular catheter
Correlative studies
Correlative studies
Correlative studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- 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
- +19 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
- Food and Drug Administration (FDA)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
Related Publications (2)
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.
PMID: 38454126DERIVEDBrown 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.
PMID: 28029927DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Christine Brown
- Organization
- City of Hope Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Behnam Badie
City of Hope Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 1, 2014
First Posted
August 5, 2014
Study Start
May 18, 2015
Primary Completion
February 8, 2021
Study Completion (Estimated)
June 8, 2026
Last Updated
September 3, 2025
Results First Posted
October 30, 2024
Record last verified: 2025-08