Recurrent GlioblastomaEarly Phase 1NCT05802693
A Study to Evaluate the Safety, Tolerance and Initial Efficacy of EGFRvIII CAR-T on Glioblastoma
A Early Phase 1 study testing Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection in people with Recurrent Glioblastoma, run by Beijing Tsinghua Chang Gung Hospital.
Trial summary
This is a single-center, open, dose-increasing study. For subjects with recurrent glioblastomaIt ,is estimated that about 22 subjects will be enrolled, The main purpose was to evaluate the safety and tolerance of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment… 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?
- Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- No sites listed yet
- Study dates
- 15 Nov 2023to 14 Nov 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- 18 ≤ age ≤ 70 years old, gender unlimited;
- Patients with recurrent glioblastoma confirmed by histology or cytology after surgery and treated with STUPP regimen (TMZ concurrent radiochemotherapy and adjuvant chemotherapy regimen);
- According to the response assessment in neuro-oncology(RANO) standard, tumor lesions with evaluable or measurable (measurable enhancement lesions are defined as enhancement lesions with clear boundary on CT or MRI, which can be developed on ≥ 2 axial films with a thickness of 5 mm, and the length and diameter of each other are more than 10 mm. If the scanning layer thickness is large, the minimum measurable lesion should be more than 2 times the layer thickness);
- Clinical pathology (immunohistochemical staining) confirmed the positive expression of EGFRvIII in the tumor;
- Sufficient peripheral blood can be obtained through vein, and there is no other contraindication for lymphocyte collection; The peripheral blood cells can be collected according to the requirements of cell preparation;
- KPS score ≥ 70 points;
- Estimated survival time ≥ 3 months;
- Subjects must give informed consent to the test before the test, and the written informed consent form shall be signed voluntarily by themselves (or their legal representatives).-
Who cannot join
- Those who have received radiotherapy after recurrence;
- They received immunosuppressive or glucocorticoid treatment within 2 weeks before enrollment;
- Those who receive live vaccine within 4 weeks before enrollment and/or plan to participate in the trial;
- He received other chemical drugs except lymphocyte clearance within 2 weeks before enrollment;
- Not recovered from the adverse events caused by previous anti-tumor treatment before enrollment (according to NCI-CTCAE v5.0, recovered to ≤ 1 level), excluding hair loss and sequelae;
- Previously received targeted drug therapy, cell therapy, gene therapy or other immunotherapy;
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- Have received organ transplantation in the past;
- Those who are unable to perform brain MRI examination;
- Any of the following exceptions occurred in the laboratory inspection:
- Blood routine test: absolute neutrophil count (ANC) < 1.5 × 10 ⁹/L, or platelet (PLT) < 80 × 10 ⁹/L, or hemoglobin (HGB) < 100 g/L;
- Coagulation function: prothrombin time (PT), or activated partial thromboplastin time (APTT), or INR > 1.5 × ULN；
- Liver function: total bilirubin (TBIL)>2 × ULN (upper limit of normal value), or alanine transferase (ALT), aspartate transferase (AST) > 3 × ULN；
- Renal function: serum creatinine (Cr) ≥ 1.5 × ULN, or glomerular filtration rate (GFR) < 60ml/min · 1.73m2;
- Subjects with active hepatitis B after treatment (HBsAg positive and HBV-DNA more than 1000 copies/ml (200 IU/ml) or higher than the lower detection limit, whichever is higher) are required to receive anti hepatitis B virus treatment during the study treatment; Active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection), human immunodeficiency virus or acquired immunodeficiency syndrome (HIV) related diseases. Note: Hepatocellular carcinoma(HCC) subjects with Hepatitis B virus(HBV) may be included in the study only after the researchers determine that their hepatitis is in a clinical stable state; No HCC subjects undergoing treatment are allowed to be enrolled with HCV;
- Cardiac ultrasound: left ventricular ejection fraction Left ventricular ejection fraction(LVEF)<50%;
- Acute bacterial or fungal infection requiring intravenous antibiotics during cell transfusion;
- Negligent compensatory heart failure (NYHA grade III and IV), unstable angina pectoris, acute myocardial infarction, persistent and clinically significant arrhythmia occurred within 3 months before enrollment;
- Those who need to inhale oxygen to maintain blood oxygen saturation above 95% before entering the group and cannot return to normal within 2 weeks;
- Having other malignant tumors and not being effectively controlled;
- Have a history of tuberculosis;
- Those who are known or expected to have allergic reactions or have a history of allergy to any component of the test treatment;
- Known contrast agent allergy;
- Have a clear history of mental disorders in the past;
- Previous history of drug abuse or drug abuse;
- Pregnant or lactating women, or those who plan to become pregnant during the study period;
- Women of childbearing age and men with fertility cannot take effective and adequate contraceptive measures (such as intrauterine devices, condoms, spermicidal gel plus condoms, diaphragms, etc.) during the period of receiving the study drug and three months after the end of the study;
- Those who participated in other clinical trials within 30 days before study enrollment;
- The investigator judged that it was not suitable to participate in this clinical trial.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: An Open Clinical Study to Evaluate the Safety, Tolerance and Initial Efficacy of Epidermal Growth Factor Receptor Variant III Chimeric Antigen Receptor T(EGFRvIII CAR-T) in the Treatment of Recurrent Glioblastoma
This is a single-center, open, dose-increasing study. For subjects with recurrent glioblastomaIt ,is estimated that about 22 subjects will be enrolled, The main purpose was to evaluate the safety and tolerance of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma.The secondary purpose is to preliminarily evaluate the anti-tumor activity of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma, and preliminarily evaluate the relationship between the clinical efficacy, safety and pharmacokinetics of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) preparation, as well as their correlation with tumor markers or other potential biomarkers.
This clinical study is an open clinical study, including dose increasing stage and expansion stage. The main objective of the study was to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) in the treatment of Glioblastoma (GBM) by local administration (Omaya capsule administration). The study will be divided into the following stages: screening stage, baseline stage, treatment stage, short-term follow-up and long-term follow-up stage.
- Conditions
- Recurrent Glioblastoma
- Being tested
- Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injectionDrug
Also called DCTY0801 Autologous T lymphocyte injection
Infusion of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) with Omaya capsule
| Study group | Role | What they receive |
|---|---|---|
| The dose increase phase of this study adopts a 3+3 half-step design | Experimental | The main research objective of active comparator is to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) injected by local administration (Omaya capsule administration) in the treatment of Glioblastoma(GBM).
Initial dose 22 × 10^6 cells will adopt accelerated titration (ATD); 60 × 10^6 cells，160 × 10^6 cells and 220 × 10^6 cells will use the BOIN method to increase the dose. The planned dose increase scheme is divided into accelerated titration stage (ATD) and BOIN stage Receives: Drug: Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Will assess dose limiting toxicity and all toxicities. Toxicity is the primary endpoint and will be assessed using the National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 . Rates and associated 95% Clopper and Pearson binomial confidence limits (95% confidence interval [CI]) will be estimated for participants' experiencing dose limiting toxicity (DLT). All toxicities and side effects will be summarized in tables by dose, time period, organ, and severity.
Measured: Up to 15 years
Dose-limiting toxicity (DLT)
A toxicity that causes side effects that are serious enough to prevent an increase in dose or level of that treatment.
Measured: Up to 28 days
Secondary outcomes (11)
T cell levels
Will assess chimeric antigen receptor (CAR) T levels and phenotype detected in peripheral blood (PB) (absolute number per ul by flow).
Will assess EGFRvIII CAR gene copies in peripheral blood (PB)（Q-PCR method ). Statistical and graphical methods will be used to describe persistence and expansion.
Measured: Up to 15 years
Cytokine levels in PB
Statistical and graphical methods will be used to describe persistence and expansion.
Measured: Up to 15 years
Disease response
By Response Assessment in Neuro-Oncology (RANO) criteria with the need for Avastin as an additional indicator of progression.
Measured: Up to 15 years
Time to progression
Progression is defined by RANO with the need for Avastin as an additional indicator of progression.
Measured: Up to 15 years
Complete response (CR)
Kaplan Meier methods will be used to estimate median CR and graph the results.
Measured: Up to 15 years
Partial Response (PR)
Kaplan Meier methods will be used to estimate median PR and graph the results.
Measured: Up to 15 years
Stable disease (SD)
Kaplan Meier methods will be used to estimate median SD and graph the results.
Measured: Up to 15 years
Progressive disease (PD)
Kaplan Meier methods will be used to estimate median PD and graph the results.
Measured: Up to 15 years
Progression free survival (PFS)
Kaplan Meier methods will be used to estimate median PFS and graph the results.
Measured: Up to 15 years
Overall survival (OS)
Kaplan Meier methods will be used to estimate median OS and graph the results.
Measured: Up to 15 years
Quality of life (QOL)
Will estimate the mean and standard error for change from baseline during treatment and post treatment in the quality of life functioning scale, symptom scale and item scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30（EORTC QLQ-C30）. Health-Related Quality of Life and Sympotoms will be assessed from the International Validation Study of the EORTC Brain Cancer Module(EORTC QLQ-BN20)
Measured: Up to 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2023
- Study start15 Nov 2023 (estimated)
- Primary completion14 Nov 2025 (estimated)
- Study completion14 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tsinghua Chang Gung Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing DCTY Biotech Co.,Ltd.
- Responsible party
- Principal investigator, Xuejun Yang, Beijing Tsinghua Chang Gung Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05802693
- Sponsor's protocol ID
- A03728
- Status last verified
- Aug 2023
- First submitted
- 16 Mar 2023
- Last updated
- 25 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Clinical Study to Evaluate the Safety, Tolerance and Initial Efficacy of Epidermal Growth Factor Receptor Variant III Chimeric Antigen Receptor T(EGFRvIII CAR-T) in the Treatment of Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT05802693
- Acronym / sponsor ID
- A03728
- Conditions
- Recurrent Glioblastoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Beijing Tsinghua Chang Gung HospitalUniversity, hospital or other
- Collaborators
- Beijing DCTY Biotech Co.,Ltd.
- Study start
- 15 Nov 2023 (estimated)
- Primary completion
- 14 Nov 2025 (estimated)
- Study completion
- 14 Nov 2025 (estimated)
- First posted
- 6 Apr 2023 (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 single-center, open, dose-increasing study. For subjects with recurrent glioblastomaIt ,is estimated that about 22 subjects will be enrolled, The main purpose was to evaluate the safety and tolerance of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma.The secondary purpose is to preliminarily evaluate the anti-tumor activity of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) in the treatment of patients with recurrent glioblastoma, and preliminarily evaluate the relationship between the clinical efficacy, safety and pharmacokinetics of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) preparation, as well as their correlation with tumor markers or other potential biomarkers.
This clinical study is an open clinical study, including dose increasing stage and expansion stage. The main objective of the study was to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) in the treatment of Glioblastoma (GBM) by local administration (Omaya capsule administration). The study will be divided into the following stages: screening stage, baseline stage, treatment stage, short-term follow-up and long-term follow-up stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| The dose increase phase of this study adopts a 3+3 half-step design | Experimental | Drug: Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injectionThe main research objective of active comparator is to observe the efficacy and safety of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T cells(EGFRvIII CAR-T cells) injected by local administration (Omaya capsule administration) in the treatment of Glioblastoma(GBM). Initial dose 22 × 10^6 cells will adopt accelerated titration (ATD); 60 × 10^6 cells，160 × 10^6 cells and 220 × 10^6 cells will use the BOIN method to increase the dose. The planned dose increase scheme is divided into accelerated titration stage (ATD) and BOIN stage |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 ≤ age ≤ 70 years old, gender unlimited;
- Patients with recurrent glioblastoma confirmed by histology or cytology after surgery and treated with STUPP regimen (TMZ concurrent radiochemotherapy and adjuvant chemotherapy regimen);
- According to the response assessment in neuro-oncology(RANO) standard, tumor lesions with evaluable or measurable (measurable enhancement lesions are defined as enhancement lesions with clear boundary on CT or MRI, which can be developed on ≥ 2 axial films with a thickness of 5 mm, and the length and diameter of each other are more than 10 mm. If the scanning layer thickness is large, the minimum measurable lesion should be more than 2 times the layer thickness);
- Clinical pathology (immunohistochemical staining) confirmed the positive expression of EGFRvIII in the tumor;
- Sufficient peripheral blood can be obtained through vein, and there is no other contraindication for lymphocyte collection; The peripheral blood cells can be collected according to the requirements of cell preparation;
Key exclusion criteria (28 listed)
- Those who have received radiotherapy after recurrence;
- They received immunosuppressive or glucocorticoid treatment within 2 weeks before enrollment;
- Those who receive live vaccine within 4 weeks before enrollment and/or plan to participate in the trial;
- He received other chemical drugs except lymphocyte clearance within 2 weeks before enrollment;
- Not recovered from the adverse events caused by previous anti-tumor treatment before enrollment (according to NCI-CTCAE v5.0, recovered to ≤ 1 level), excluding hair loss and sequelae;
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 |
|---|---|---|
| Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injectionAlso: DCTY0801 Autologous T lymphocyte injectionInfusion of Epidermal Growth Factor Receptor Variant III Chimeric antigen receptor T(EGFRvIII CAR-T) with Omaya capsule | Drug | The dose increase phase of this study adopts a 3+3 half-step design |
Primary outcome
Incidence of adverse events
Time frame: Up to 15 years
Will assess dose limiting toxicity and all toxicities. Toxicity is the primary endpoint and will be assessed using the National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 . Rates and associated 95% Clopper and Pearson binomial confidence limits (95% confidence interval [CI]) will be estimated for participants' experiencing dose limiting toxicity (DLT). All toxicities and side effects will be summarized in tables by dose, time period, organ, and severity.
Dose-limiting toxicity (DLT)
Time frame: Up to 28 days
A toxicity that causes side effects that are serious enough to prevent an increase in dose or level of that treatment.
11 secondary outcomes
T cell levels
Time frame: Up to 15 years
Cytokine levels in PB
Time frame: Up to 15 years
Disease response
Time frame: Up to 15 years
Time to progression
Time frame: Up to 15 years
Complete response (CR)
Time frame: Up to 15 years
Partial Response (PR)
Time frame: Up to 15 years
Stable disease (SD)
Time frame: Up to 15 years
Progressive disease (PD)
Time frame: Up to 15 years
Progression free survival (PFS)
Time frame: Up to 15 years
Overall survival (OS)
Time frame: Up to 15 years
Quality of life (QOL)
Time frame: Up to 15 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- 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. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Targeted Epidermal Growth Factor Receptor Variant III(EGFRvIII) autochimeric antigen receptor T cell injection in people with Recurrent Glioblastoma, run by Beijing Tsinghua Chang Gung Hospital.
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 8 inclusion and 28 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: status not confirmed, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yang Xuejun (13011329950, yxja03728@btch.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 15 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 25 Aug 2023.