Recurrent GlioblastomaPhase 1/2NCT04077866
B7-H3 CAR-T for Recurrent or Refractory Glioblastoma
A Phase 1/2 study testing Temozolomide and B7-H3 CAR-T in people with Recurrent Glioblastoma and Refractory Glioblastoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 3 sites in China.
Trial summary
This is a randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent Glioblastoma, Refractory Glioblastoma
- What is being tested?
- Temozolomide and B7-H3 CAR-T
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesChina
- Study dates
- 1 Jun 2023to 1 Aug 2025
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented informed consent of the participant and/or legally authorized representative.
- Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).
- Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score >= 50).
- Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.
- Suitable for the surgery of the placement of the Ommaya catheter.
- Eastern Cooperative Oncology Group (ECOG) =0 or 1 (need to be confirmed before intratumoral or intracerebroventricular injection)
Show all 19Show fewer
- >= 8 weeks after completion of front-line radiation therapy
- >= 6 weeks after completion of nitrourea chemotherapy
- >= 14 days after completion of Temozolomide or other chemotherapy
- 2 weeks of wash-out time after completion of targeted therapy with related adverse events (AE) on baseline (4 weeks for Bevacizumab). Patients with other chronic AEs are in the investigator's judgement
- Blood cell count： White blood count (WBC) >= 2000/μL；Neutrophil count >= 1500/μL；Platelets >= 100 x 103/μL；Hemoglobin >= 9.0 g/dL
- Serum Creatinine <= 1.5×ULN or Creatinine Clearance Rate (Cockcroft and Gault) > 30 mL/min/1.73 m2
- Alanine Transaminase (ALT) <= 5×ULN and total bilirubin < 2.0mg/dL
- Lung function: Oxygen (O2) saturation >= 92% on room air and < CTCAE grade 1 dyspnea
- Heart function: Left ventricular ejection fraction (LVEF) >= 40% by multigated acquisition (MUGA) scan or echocardiogram
- Normal coagulation function: prothrombin time (PT)，activated partial thromboplastin time (APTT) and international normalized ratio (INR)
- Good blood vessel condition for leukapheresis
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity within one year after B7-H3 CAR-T infusion
Who cannot join
- Other active malignancy in the past 2 years except non-melanoma skin cancer, completely surgical removed low grade tumor, post-therapeutic limited-stage prostate cancer, biopsy confirmed in situ cervical carcinoma, PAP test confirmed squamous intraepithelial lesions
- Participant is undergoing or planning to take other anti-tumor therapies
- Participant is systematic steroid-dependent, or is expecting to be treated with systematic steroid
- Active immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection
- Active infection from fungi, bacteria and/or viruses
- Known history of the following cardiac diseases in the past 6 months: New York Heart Association (NYHA) defined grade III or IV heart failure, cardiac angioplasty, myocardial infarction, unstable angina and other clinically significant heart diseases
Show all 17Show fewer
- Known history and/or clinically evident central nerve system diseases: seizure, epileptic seizure, aphasia, paralysis, stroke, severe brain damage, dementia, Parkinson's Disease, cerebellar diseases, organic brain syndrome and psychiatric disorders
- Autoimmune diseases
- Pregnant or breastfeeding females
- Therapeutic doses of corticosteroid within 7 days before leukapheresis or 72 hours before B7-H3 CAR-T infusion
- Cytotoxic chemotherapy without lymphocytotoxicity within 1 week before leukapheresis except that the treatment has been stopped for more than 3 half-lives of the drug
- Lymphocytotoxic chemotherapy (cyclophosphamide, Ifosfamide and bendamustine) within 2 weeks before leukapheresis
- Other clinical trials drugs within 4 weeks before leukapheresis except that the drug has no effect or the disease has progressed, and the treatment has been stopped for more than 3 half-lives of the drug
- Radiotherapy within 6 weeks before leukapheresis
- Prior trials of CAR-T or other cell therapy
- Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
the Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
Jianmin Zhang, MD, 86-13805722695, 2307010@zju.edu.cn
- Not yet recruiting
Huzhou Central Hospital
Huzhou, Zhejiang, 313003
Zhongzhou Su, MD
- Not yet recruiting
Ningbo Yinzhou People's Hospital
Ningbo, Zhejiang, 315040
Feng Gao, MD
About this study
Official title: B7-H3-Targeted Chimeric Antigen Receptor (CAR) T Cells in Treating Patients With Recurrent or Refractory Glioblastoma
This is a randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. The antigen B7-H3 is highly expressed in glioblastoma of a subset of patients. B7-H3 CAR-T, made from isolated patient peripheral blood mononuclear cells, can specifically attack patient glioblastoma cells that expressing B7-H3.
Read the detailed description
Background
- B7-H3 is expressed in 70% of patients with glioblastoma
- B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for CAR-T therapy
- The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency.
Objectives
- To evaluate the safety and tolerability intratumoral/intracerebroventricular injection of B7-H3 CAR-T when used in between Temozolomide cycles
- To compare the overall survival (OS) and progression-free survival (PFS) of R/R GBM patients treated with B7-H3 CAR-T in between Temozolomide cycles vs Temozolomide alone
- To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles
Design
- Experimental group: Patients autologous T cells are activated and transduced with retrovirus containing B7-H3 CAR. CAR-T cells are expanded ex vivo and infused back to patients via intratumoral or intracerebroventricular injection through an Ommaya catheter. 3 injections of CAR-T are planned at two different doses with 1-2 weeks intervals. The CAR-T injections occur in between Temozolomide (TMZ) cycles. Temozolomide treatment during the cycles of CAR-T injections will be stopped and resumed next cycle. Patients may receive additional CAR-T cycles at the discretion of the principal investigator and oncologist.
- Control group: Patients will receive regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval.
- Conditions
- Recurrent Glioblastoma, Refractory Glioblastoma
- Being tested
- Temozolomide, B7-H3 CAR-T
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called TMZ
Temozolomide is an FDA-approved drug that is given to patients
B7-H3 CAR-TBiological
B7-H3-targeting CAR-T cells derived from patient own peripheral blood mononuclear cells will be given to patients via intracerebral injection though an Ommaya catheter
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide alone | Active comparator | Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped. Receives: Drug: Temozolomide |
| Temozolomide + B7-H3 CAR-T | Experimental | Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped.
The B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide treatment in the cycles of B7-H3 CAR-T treatment will be stopped. Receives: Drug: Temozolomide; Biological: B7-H3 CAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Kaplan Meier methods will be used to estimate median OS
Measured: 2 years, up to 15 years if necessary
Secondary outcomes (6)
Incidence and type of adverse events
Number of Participants With Treatment-Related Adverse Events and Types of adverse events as Assessed by CTCAE v4.0
Measured: 12 weeks
Maximum tolerated dose (MTD)
The highest dose of B7-H3 CAR-T that does not cause targeted dose-limiting toxicity
Measured: 12 weeks
Progression-free survival (PFS)
Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria
Measured: 2 years, up to 15 years if necessary
Peak Concentration (Cmax) of B7-H3 CAR-T
Peak Concentration (Cmax) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)
Measured: 12 weeks
Area under the concentration versus time curve (AUC) of B7-H3 CAR-T
Area under the concentration versus time curve (AUC) of B7-H3 CAR-T in peripheral blood (PB) and cerebral spinal fluid (CSF)
Measured: 12 weeks
Disease response (ORR, CR, PR, DOR)
Objective Response Rate (ORR) will be assessed by comparison with baseline magnetic resonance imaging by RANO. Complete Response (CR) is disappearance of all measurable and non-measurable disease for at least 4 weeks. Partial Response (PR) is >/= 50% decrease in lesions for at least 4 weeks. Duration of Response (DOR) is the time between the initial response to the treatment and subsequent disease progression.
Measured: 2 years, up to 15 years if necessary
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start1 Jun 2023 (estimated)
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ningbo Yinzhou People's Hospital, Huizhou Municipal Central Hospital, BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04077866
- Sponsor's protocol ID
- SAHZJU-RCT-BP102
- Status last verified
- Dec 2022
- First submitted
- 26 Aug 2019
- Last updated
- 28 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.
PubMed 35468680
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B7-H3-Targeted Chimeric Antigen Receptor (CAR) T Cells in Treating Patients With Recurrent or Refractory Glioblastoma
- ClinicalTrials.gov ID
- NCT04077866
- Acronym / sponsor ID
- SAHZJU-RCT-BP102
- Conditions
- Recurrent Glioblastoma, Refractory Glioblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Ningbo Yinzhou People's Hospital, Huizhou Municipal Central Hospital, BoYuan RunSheng Pharma (Hangzhou) Co., Ltd.
- Study start
- 1 Jun 2023 (estimated)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 4 Sep 2019 (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 randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. The antigen B7-H3 is highly expressed in glioblastoma of a subset of patients. B7-H3 CAR-T, made from isolated patient peripheral blood mononuclear cells, can specifically attack patient glioblastoma cells that expressing B7-H3.
Detailed description
Background
- B7-H3 is expressed in 70% of patients with glioblastoma
- B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for CAR-T therapy
- The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency.
Objectives
- To evaluate the safety and tolerability intratumoral/intracerebroventricular injection of B7-H3 CAR-T when used in between Temozolomide cycles
- To compare the overall survival (OS) and progression-free survival (PFS) of R/R GBM patients treated with B7-H3 CAR-T in between Temozolomide cycles vs Temozolomide alone
- To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles
Design
- Experimental group: Patients autologous T cells are activated and transduced with retrovirus containing B7-H3 CAR. CAR-T cells are expanded ex vivo and infused back to patients via intratumoral or intracerebroventricular injection through an Ommaya catheter. 3 injections of CAR-T are planned at two different doses with 1-2 weeks intervals. The CAR-T injections occur in between Temozolomide (TMZ) cycles. Temozolomide treatment during the cycles of CAR-T injections will be stopped and resumed next cycle. Patients may receive additional CAR-T cycles at the discretion of the principal investigator and oncologist.
- Control group: Patients will receive regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temozolomide alone | Active comparator | Drug: TemozolomideTemozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped. |
| Temozolomide + B7-H3 CAR-T | Experimental | Drug: Temozolomide, Biological: B7-H3 CAR-TTemozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped. The B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide treatment in the cycles of B7-H3 CAR-T treatment will be stopped. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Documented informed consent of the participant and/or legally authorized representative.
- Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).
- Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score >= 50).
- Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.
- Suitable for the surgery of the placement of the Ommaya catheter.
Key exclusion criteria (17 listed)
- Other active malignancy in the past 2 years except non-melanoma skin cancer, completely surgical removed low grade tumor, post-therapeutic limited-stage prostate cancer, biopsy confirmed in situ cervical carcinoma, PAP test confirmed squamous intraepithelial lesions
- Participant is undergoing or planning to take other anti-tumor therapies
- Participant is systematic steroid-dependent, or is expecting to be treated with systematic steroid
- Active immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection
- Active infection from fungi, bacteria and/or viruses
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 |
|---|---|---|
| TemozolomideAlso: TMZTemozolomide is an FDA-approved drug that is given to patients | Drug | Temozolomide + B7-H3 CAR-T, Temozolomide alone |
| B7-H3 CAR-TB7-H3-targeting CAR-T cells derived from patient own peripheral blood mononuclear cells will be given to patients via intracerebral injection though an Ommaya catheter | Biological | Temozolomide + B7-H3 CAR-T |
Primary outcome
Overall survival (OS)
Time frame: 2 years, up to 15 years if necessary
Kaplan Meier methods will be used to estimate median OS
6 secondary outcomes
Incidence and type of adverse events
Time frame: 12 weeks
Maximum tolerated dose (MTD)
Time frame: 12 weeks
Progression-free survival (PFS)
Time frame: 2 years, up to 15 years if necessary
Peak Concentration (Cmax) of B7-H3 CAR-T
Time frame: 12 weeks
Area under the concentration versus time curve (AUC) of B7-H3 CAR-T
Time frame: 12 weeks
Disease response (ORR, CR, PR, DOR)
Time frame: 2 years, up to 15 years if necessary
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2022.
- Derived from this study: PubMed 35468680Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.
- 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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Temozolomide and B7-H3 CAR-T in people with Recurrent Glioblastoma and Refractory Glioblastoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 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 28 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Jianmin Zhang, MD (+86-13805722695, 2307010@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: 2 years, up to 15 years if necessary). 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 NCT04077866, which also lists 1 linked publication.
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 Dec 2022.