Brain and Nervous SystemPhase 1NCT05474378
B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Recurrent Glioblastoma Multiforme
A Phase 1 study testing B7-H3CART in people with Brain and Nervous System, run by Stanford University at 1 site in United States.
Trial summary
This is an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Nervous System
- What is being tested?
- B7-H3CART
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jul 2022to Feb 2027
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features, tested as IDH wild-type, as per revised WHO 2021 criteria. Patients must also have evidence of tumor recurrence/progression by MRI (RANO criteria) after standard front-line therapy. b. First recurrence or progressive disease after a standard line therapy.
- Resectable disease: Resection is being considered as part of the standard of care for the patient and it is thought that it is feasible that a majority of contrast-enhancing tumor mass/signal can be resected.
- Patients must be between the ages of 18 and 75 years old (inclusive).
- Karnofsky Performance score ≥ 60.
- Use of steroids must be limited to ≤ 4 mg of decadron daily.
- Adequate organ function at time of screening visit including:
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- Hgb ≥ 12 g/dL (male) or ≥ 11.5 g/dL (females)
- ANC ≥ 1500/uL
- Platelets ≥ 100,000/uL
- Absolute lymphocyte count ≥150/uL
- Serum Creatinine ≤ 1.5mg/dl; Cr clearance should be ≥ 50 mL/min
- Serum AST and ALT ≤ 3x ULN (Grade 1)
- Total Bilirubin ≤ 1.5 X ULN
- PT or PTT ≤ 1.25 X ULN
- Cardiac ejection fraction ≥45% without signs of physiologically significant pericardial effusion or clinically significant ECG findings.
- Baseline oxygen saturation > 92% on room air
- Subjects of child-bearing or child-fathering potential must be willing to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 4 months following the last CAR T cell infusion or as long as B7-H3CART are detectable in peripheral blood or CSF.
- All female subjects of childbearing age must have a negative blood or urine pregnancy test.
- Ability to understand and willingness to sign a written informed consent document.
- Must be willing and able to comply with procedures, return visits and evaluations at Stanford Health Care while on this protocol.
- Prior Therapy:
- At least 6 weeks following completion of front-line radiation therapy.
- At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.
- At least 4 weeks from bevacizumab treatment, which can be used only for radiation necrosis or pseudo-progression.
- Prior cytotoxic chemotherapy, radiation, or other anticancer therapies including investigational agents discontinued at least 4 weeks prior to Day 1 of treatment.
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia).
Who cannot join
- Pregnant or patients who are breastfeeding.
- Prior or concurrent treatment with Avastin (bevacizumab) for the purposes of recurrent disease. Avastin (bevacizumab) may have been used for radiation necrosis.
- Prior exposure to chimeric antigen receptor (CAR) based therapies.
- Known sensitivity or allergy to any agents/reagents used in this study.
- Requires current anticoagulation therapy that cannot be safely paused for surgical resection and Ommaya access.
- Prior malignancy except previously diagnosed and definitively treated more than 3 years prior to trial or whose prognosis is deemed good enough to not warrant surveillance.
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- Clinical evidence of significant increased intracranial pressure (i.e. impending herniation) or uncontrolled seizures.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
- Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- Primary immunodeficiency or history of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
- Significant medical diseases or conditions, including poorly controlled conditions: i.e. hypertension, cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, pulmonary fibrosis, inflammatory disorders, immunodeficiency (e.g., HIV infection), immune compromised for reasons other than malignancy (e.g., chronic corticosteroid therapy or other immunosuppressive therapy), renal failure including patients requiring dialysis, liver dysfunction, second malignancy (except treated basal cell or localized squamous cell skin carcinomas), or active infection.
- History of bone marrow or stem cell transplantation.
- In the investigator's judgment, the subject is unlikely to complete all protocol- required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stanford Cancer Institute
Palo Alto, California, 94305
Kelly Tanner, 650-724-5361, ketanner@stanford.edu
Gordon Li, MD
About this study
Official title: Phase I Clinical Trial of Locoregionally (LR) Delivered Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Adults With Recurrent Glioblastoma Multiforme (GBM)
This is an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design.
- Conditions
- Brain and Nervous System
- Being tested
- B7-H3CART
- Medical subject headings
- Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B7-H3CARTDrug
Also called B7H3-CAR T
B7-H3CART will be administered administered locoregionally (either ICV or both ICV and intratumorally (IT)) at one of the following doses:
Dose Level -1: 5 x 10^6 CAR+ cells (+/- 20%) Dose Level 1: 10 x 10^6 CAR+ cells (+/- 20%) Dose Level 2: 25 x 10^6 CAR+ cells (+/- 20%) Dose Level 3: 50 x 10^6 CAR+ cells (+/- 20%) Dose Level 4: 100 x 10^6 CAR+ cells (+/- 20%)
B7-H3CART Dose Dose Level -1 (DL-1): 5 x 106 B7-H3CART+ cells (± 20%) Dose Level 1 (DL 1): 10 x 106 B7-H3CART+ cells (± 20%) Dose Level 2 (DL2): 25 x 106 B7-H3CART+ cells (± 20%) Dose Level 3 (DL3): 50 x 106 B7-H3CART+ cells (± 20%) Dose Level 4 (DL4): 100 x 106 B7-H3CART+ cells (± 20%)
Repeated every 28 days (-7 / +14 days) as long as infusion criteria are met for a total of 6 doses, with an option for an additional 6 doses, up to a total of 12.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | All subjects will be assigned to a dose level. Does escalation will proceed sequentially via a standard 3+3 dose escalation design in subjects who receive at least one infusion of B7-H3CART. Each dose level will include 3 to 6 subjects, starting at Dose Level 1. If Dose Level 1 is considered too toxic, the dose may be de-escalated to Dose Level -1. If Dose Level 4 is completed with no dose limiting toxicity (DLT) in six subjects, a maximum tolerated dose (MTD) may not be determined, and Dose Level 4 will instead be the maximum administered dose (MAD). T Receives: Drug: B7-H3CART |
| Dose Expansion | Experimental | After Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is established, a total of 12 evaluable subjects (including the 6 subjects infused during the dose escalation phase) will be enrolled at the RP2D to further explore safety of repeat administrations at MTD/RP2D and conduct a preliminary assessment of benefit. Receives: Drug: B7-H3CART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of successful manufacturing product (B7-H3CART) that met minimum assigned dose level range
Defined by the frequency of successful manufacturing runs of B7-H3CART that meet the established IND release criteria for the targeted dose level.
Measured: 5 years
Maximum Tolerated Dose (MTD) or Recommended phase 2 dose (RP2D)
Defined by the frequency of subjects experiencing dose limiting toxicity (DLT) after initial infusion
Measured: 5 years
Secondary outcomes (5)
Cumulative Safety of B7-H3CART
At each dose level, incidence and severity of DLT, adverse events and serious adverse events after initial and subsequent infusions of LR B7-H3CART infusion. The definition of DLT in these studies uses NCI's Common Terminology Criteria for Adverse Events (CTCAEv5.0)
Measured: 5 years
Immunotherapy Response Assessment in Neuro-oncology (iRANO) in subjects with recurrent IDH wild-type GBM
iRano response criteria will be measured by complete response, partial response, minor response, stable disease, progressive disease,
Measured: 5 years
Time to progression (TTP)
the time from the start (surgical resection) to the date of radiographic progression (death is censored)
Measured: 5 years
Median overall survival (OS)
time from the date of initial disease diagnosis to the date of death from any cause
Measured: 5 years
Percentage of subjects able to receive at least three (3) doses of B7-H3CART
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study start12 Jul 2022
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Nervous SystemStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), Parker Institute for Cancer Immunotherapy
- Responsible party
- Sponsor
- Investigators
- Reena Thomas, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05474378
- Sponsor's protocol ID
- IRB-65002
- Other IDs
- NCI-2022-06043
- Status last verified
- Sep 2026
- First submitted
- 22 Jul 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Locoregionally (LR) Delivered Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Adults With Recurrent Glioblastoma Multiforme (GBM)
- ClinicalTrials.gov ID
- NCT05474378
- Acronym / sponsor ID
- IRB-65002
- Conditions
- Brain and Nervous System
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), Parker Institute for Cancer Immunotherapy
- Study start
- 12 Jul 2022 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 26 Jul 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 an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: B7-H3CARTAll subjects will be assigned to a dose level. Does escalation will proceed sequentially via a standard 3+3 dose escalation design in subjects who receive at least one infusion of B7-H3CART. Each dose level will include 3 to 6 subjects, starting at Dose Level 1. If Dose Level 1 is considered too toxic, the dose may be de-escalated to Dose Level -1. If Dose Level 4 is completed with no dose limiting toxicity (DLT) in six subjects, a maximum tolerated dose (MTD) may not be determined, and Dose Level 4 will instead be the maximum administered dose (MAD). T |
| Dose Expansion | Experimental | Drug: B7-H3CARTAfter Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is established, a total of 12 evaluable subjects (including the 6 subjects infused during the dose escalation phase) will be enrolled at the RP2D to further explore safety of repeat administrations at MTD/RP2D and conduct a preliminary assessment of benefit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically confirmed high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features, tested as IDH wild-type, as per revised WHO 2021 criteria. Patients must also have evidence of tumor recurrence/progression by MRI (RANO criteria) after standard front-line therapy. b. First recurrence or progressive disease after a standard line therapy.
- Resectable disease: Resection is being considered as part of the standard of care for the patient and it is thought that it is feasible that a majority of contrast-enhancing tumor mass/signal can be resected.
- Patients must be between the ages of 18 and 75 years old (inclusive).
- Karnofsky Performance score ≥ 60.
- Use of steroids must be limited to ≤ 4 mg of decadron daily.
Key exclusion criteria (13 listed)
- Pregnant or patients who are breastfeeding.
- Prior or concurrent treatment with Avastin (bevacizumab) for the purposes of recurrent disease. Avastin (bevacizumab) may have been used for radiation necrosis.
- Prior exposure to chimeric antigen receptor (CAR) based therapies.
- Known sensitivity or allergy to any agents/reagents used in this study.
- Requires current anticoagulation therapy that cannot be safely paused for surgical resection and Ommaya access.
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 |
|---|---|---|
| B7-H3CARTAlso: B7H3-CAR TB7-H3CART will be administered administered locoregionally (either ICV or both ICV and intratumorally (IT)) at one of the following doses: Dose Level -1: 5 x 10^6 CAR+ cells (+/- 20%) Dose Level 1: 10 x 10^6 CAR+ cells (+/- 20%) Dose Level 2: 25 x 10^6 CAR+ cells (+/- 20%) Dose Level 3: 50 x 10^6 CAR+ cells (+/- 20%) Dose Level 4: 100 x 10^6 CAR+ cells (+/- 20%) B7-H3CART Dose Dose Level -1 (DL-1): 5 x 106 B7-H3CART+ cells (± 20%) Dose Level 1 (DL 1): 10 x 106 B7-H3CART+ cells (± 20%) Dose Level 2 (DL2): 25 x 106 B7-H3CART+ cells (± 20%) Dose Level 3 (DL3): 50 x 106 B7-H3CART+ cells (± 20%) Dose Level 4 (DL4): 100 x 106 B7-H3CART+ cells (± 20%) Repeated every 28 days (-7 / +14 days) as long as infusion criteria are met for a total of 6 doses, with an option for an additional 6 doses, up to a total of 12. | Drug | Dose Expansion, Dose escalation |
Primary outcome
Number of successful manufacturing product (B7-H3CART) that met minimum assigned dose level range
Time frame: 5 years
Defined by the frequency of successful manufacturing runs of B7-H3CART that meet the established IND release criteria for the targeted dose level.
Maximum Tolerated Dose (MTD) or Recommended phase 2 dose (RP2D)
Time frame: 5 years
Defined by the frequency of subjects experiencing dose limiting toxicity (DLT) after initial infusion
5 secondary outcomes
Cumulative Safety of B7-H3CART
Time frame: 5 years
Immunotherapy Response Assessment in Neuro-oncology (iRANO) in subjects with recurrent IDH wild-type GBM
Time frame: 5 years
Time to progression (TTP)
Time frame: 5 years
Median overall survival (OS)
Time frame: 5 years
Percentage of subjects able to receive at least three (3) doses of B7-H3CART
Time frame: 5 years
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 15 Sep 2026.
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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.
Reena Thomas, MD, PhD principal investigator
Stanford University
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 B7-H3CART in people with Brain and Nervous System, run by Stanford University 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 26 inclusion and 13 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 15 Sep 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?
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 Kelly Tanner (650-724-5361, ketanner@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of successful manufacturing product (B7-H3CART) that met minimum assigned dose level range (time frame: 5 years). 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?
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 15 Sep 2026.