GBMEarly Phase 1CSAγδTBMGNCT06396481
Clinical Study of Allogeneic Vγ9Vδ2 T Cells in the Treatment of Brain Malignant Glioma
A Early Phase 1 study testing Vγ9Vδ2 T cell in people with GBM and DIPG Brain Tumor, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
Primary brain malignant tumor has become the first lethal tumor in children and young adults, and the treatment is limited, and the prognosis of patients is poor. According to the classification of the World Health Organization, glioblastoma is divided into grade II, III and IV gliomas; The higher the degree of… Read more about this study
- Who is it for?
- Ages 4 years and olderHealthy volunteers can take part
- Conditions the study is for
- GBM, DIPG Brain Tumor, Medulloblastoma
- What is being tested?
- Vγ9Vδ2 T cell
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2024to 30 Dec 2027
- Phase
- Early 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 4 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients with clinically diagnosed malignant brain glioma in an important structural area (WHO Grade IV);
- Patients with poor postoperative effect or ineffective guidelines for conventional treatment
- Age ≥4 years old, male or female;
- KPS score ≥70;
- Normal bone marrow reserve function and normal liver and kidney function (as evidenced by the following laboratory tests prior to initial Vγ9Vδ2 T cell therapy) :
- Neutrophil absolute value ≥ 1,500/mm3;
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- hemoglobin 10g/dL;
- Platelet count \> 100,000/mm3;
- Glutamic pyruvic transaminase/Glutamic oxalacetic transaminase \< 2.5 x ULN;
- Serum creatinine 1.5×ULN;
- Total bilirubin levels \< 1.5 x ULN.
- No obvious genetic diseases;
- Normal cardiac function, cardiac ejection index > 55%;
- Suitable for implantation of Ommaya capsule in ventricle or cavity;
- No bleeding and coagulation disorders;
- Women of reproductive age (15-49 years) must undergo a negative pregnancy test within 7 days before starting treatment and use contraception during the clinical trial period and within 3 months after the last cell transfusion;
- Sign the informed consent form.
Who cannot join
- Pregnant and lactating women;
- Organ failure;
- Heart: Grade III and grade IV;
- Liver: Level C of the Child-Turcotte liver function scale;
- Kidney: renal failure and uremia stage;
- Lungs: Symptoms of severe respiratory failure;
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- Brain: A person with a disorder of consciousness.
- Patients with a history of organ transplantation;
- Uncontrollable infectious disease or other serious illness, including but not limited to infection (such as HIV positive), congestive heart failure, unstable angina pectoris, arrhythmia, psychosis, or restrictive social environment or what the attending physician considers to be an unpredictable risk;
- Patients with systemic autoimmune disease or immunodeficiency;
- Patients with allergic constitution;
- Use of systemic steroid drugs;
- Have a chronic disease that requires the use of immune agents or hormone therapy;
- Prior treatment with any other immune cell;
- Have participated in other clinical trials within the past 30 days;
- The researchers believe that other reasons are not suitable for clinical trials
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Tao Sun, 8613331190858, suntao@bjtth.org
Tao Sun
About this study
Primary brain malignant tumor has become the first lethal tumor in children and young adults, and the treatment is limited, and the prognosis of patients is poor. According to the classification of the World Health Organization, glioblastoma is divided into grade II, III and IV gliomas; The higher the degree of malignancy, the worse the clinical outcome. Among them, the most malignant, most lethal, and most common types of tumors include supratentorial glioblastoma, diffuse endopontine glioma (DIPG), medulloblastoma, and ependymoma. Its high malignancy is mainly manifested in three aspects: extremely rapid growth and obvious invasion; The operation is not easy to remove all; The tumor has a tendency of recurrence and disseminated implantation. It can occur with children and adults of all ages. At present, surgery combined with chemoradiotherapy is the main treatment, but the therapeutic effect is not good. Studies have shown that glioblastoma, as the most common primary brain malignant tumor in adults, after standard surgery, radiotherapy and chemotherapy, the median survival time is less than 15 months, and the overall five-year survival rate is only 5.4%. Even after receiving new and expensive Tumor-treating fields, the median survival time is less than 21 months. The median survival time of DIPG patients is generally less than 1 year, and the 5-year survival rate is less than 5%. The average 5-year survival rate of medulloblastoma and anaplastic ependymoma is 40%~60%. Innovative treatments are urgently needed. Immunotherapy based on Vγ9Vδ2 T cells has become a promising research direction in recent years. Its unique phosphine antigen recognition does not depend on major histocompatibility complex (MHC), easy to allograft and other advantages. Making it one of the most promising cell therapies. Brain glioma has abnormal cholesterol metabolism and phosphine antigen accumulation, which is easily sensed by Vγ9Vδ2 T cells. Therefore, the clinical exploration of Vγ9Vδ2 T cells for glioma is of great significance to both the scientific and clinical communities.
Read the detailed description
Research purpose
- Main purpose: To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy.
- Secondary Purpose: To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma (WHO IV).
- Explore goals:
To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion. To investigate the immunological dynamics of Vγ9Vδ2 T cells after reinfusion. To explore biomarkers that might predict the clinical efficacy of Vγ9Vδ2 T cell therapy.
Research design types, principles and test steps
- Research design This is an exploratory clinical trial. It is planned to enroll 50 patients with malignant glioma (WHO Grade IV) in the Department of Neurosurgery of Beijing Tiantan Hospital to conduct a single-center, single-arm open phase I clinical trial. To evaluate the safety, feasibility, and efficacy of allogeneic Vγ9Vδ2 T cell infusion regimen in the treatment of malignant brain gliomas (WHO Grade IV). The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the cell transfusion volume was successively increased according to the doses of 1x107, 3x107, 1x108 and 3x108 per dose to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. At the same time, patients who failed to complete at least one course of precision treatment for any reason after enrollment were included in the internal control group, and patients who met the admission criteria of this study but did not participate in this study were included in the external control group, with a total of 25 cases.
- Sample size and research plan After signing the informed consent form (ICF), subjects will complete the screening period assessment according to the trial plan process sheet. Patients can be combined with the chemotherapy drug temozolomide according to the specific condition.
Recruit 20 healthy donors to provide peripheral blood. After the donors sign the informed consent, they will complete the evaluation and collection of peripheral blood according to the procedure table of the trial plan.
After screening qualified donors, it is necessary to arrange monopexing as soon as possible. The full name of mononuclear cell collection is peripheral blood mononuclear cell collection. In this study, blood cell separation will be used for mononuclear cell collection.
Monofrequency: ECG monitoring was performed before and during monofrequency, and was recorded once an hour from the beginning until the end of monofrequency. The collection time must record the circulation amount, collection volume, and collection time in a timely manner. Information on the preparation of single samples and Vγ9Vδ2 T cells was collected and recorded. If the donor does not consent to the continued use of its Vγ9Vδ2 T cells in this study, the study will be destroyed in accordance with the standard procedures prescribed by national law.
At least 15 patients with malignant brain glioma (WHO Grade IV) were initially planned to be enrolled using a staggered dosing strategy. Subject 1 and 2, and subject 2 and 3 must be monitored at least 2 weeks apart. The number of allogeneic Vγ9Vδ2 T cells was increased at each dose of 1×107, 3×107, 1×108, and 3x108 to observe their tolerance and safety. Short-term safety evaluation was performed 2-3 days after each course of cell infusion. After the treatment, according to the number of successfully prepared allogeneic Vγ9Vδ2 T cells, the study doctor can choose to continue to give cell transfusion for multiple courses according to the clinical condition of the subjects.
Further enrollment of 10 patients with malignant brain glioma (WHO Grade IV) is planned for dose-extension therapy at the optimal dose obtained above to observe tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Short-term safety evaluation was performed 2-3 days after each course of cell infusion. After the end of 3 courses, the number of successfully prepared Vγ9Vδ2 T cells can also be selected by the research doctor according to the clinical condition of the subjects to continue to give cell transfusion for multiple courses. Patients who failed to complete at least one course of precision treatment for any reason after enrollment were included in the internal control group, and patients who met the admission criteria of this study but did not participate in this study were included in the external control group, with a total of 25 cases.
Follow-up was performed at 30 days, 2 months, 3 months, 6 months, 9 months, and 12 months after the first cell reinfusion, or early withdrawal from the study, and efficacy was assessed at each follow-up.
The end of the trial was defined as withdrawal of informed consent by the last subject, termination of treatment or withdrawal from the trial, loss of follow-up or death, completion of 1 year of follow-up, or early termination of the study, whichever occurred first.
The trial may be terminated prematurely at any time for any reason attributable to the Sponsor. If necessary, the subject should have an end-of-treatment visit as soon as possible.
- Research methods Vγ9Vδ2 T cell therapy program
This is an exploratory clinical trial. It is planned to enroll 50 patients with malignant glioma (WHO Grade IV) in the Department of Neurosurgery of Beijing Tiantan Hospital to conduct a single-center, single-arm open phase I clinical trial. To evaluate the safety, feasibility, and efficacy of allogeneic Vγ9Vδ2 T cell infusion regimen in the treatment of malignant brain gliomas (WHO Grade IV).
The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4.
The study was a single-arm, single-center intervention Phase I clinical study. The overall study was carried out in two steps:
- Uphill phase: At least 15 patients with malignant glioma (WHO Grade IV) were initially planned to be enrolled. According to the 3+3 design, the amount of cell transfusion was increased successively according to the doses of 1x107, 3x107, 1x108 and 3x108 per dose to observe the tolerance and safety of the cells.
- Expansion stage: 10 patients with malignant brain glioma (WHO Grade IV) are planned to be enrolled for dose expansion therapy according to the optimal dose obtained in the climbing stage, so as to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses.
- Conditions
- GBM, DIPG Brain Tumor, Medulloblastoma
- Being tested
- Vγ9Vδ2 T cell
- Keywords
- malignant glioma, Vγ9Vδ2 T
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Medulloblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vγ9Vδ2 T cellBiological
The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4.
| Study group | Role | What they receive |
|---|---|---|
| To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy. | Experimental | The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. Receives: Biological: Vγ9Vδ2 T cell |
| To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma | Experimental | The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. Receives: Biological: Vγ9Vδ2 T cell |
| To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion. | Experimental | The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. Receives: Biological: Vγ9Vδ2 T cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety evaluation
The study will collect all adverse events that occurred after participants initiated leukocyte monopexy to Vγ9Vδ2 T cell therapy for a specified period of time or until disease progression. Safety assessment tests include: blood oxygen saturation should not be lower than 80mmHg; The ECG results of heart rate and ECG should be normal sinus rhythm. Blood biochemical examination of white blood cells should be maintained at 4000-10000/μL level; IL6 should be less than 200pg/mL. Safety assessment was performed according to the study protocol one day before each infusion of Vγ9Vδ2 T cells and one week after each infusion. Safety assessment tests include: blood oxygen saturation should not be lower than 80mmHg; The ECG results of heart rate, PR interval, RR interval, QRS, QT interval, QTcF and ECG should be normal sinus rhythm. Blood biochemical examination of white blood cells should be maintained at 4000-10000/μL level; IL6 should be less than 200pg/mL.
Measured: up to 12 months
Secondary outcomes (1)
curative effect appraising
Primary endpoints typically included MRI measurements of enhanced lesions in the lumen before and each week after reinfusion using RANO criteria: complete response (disappearance of enhanced lesions), partial response (reduction > 30%), disease stabilization (reduction <30% or increase < 20%), or disease progression (lesions > 20% or emergence of new lesions).
Survival analysis: Overall survival (OS), which measures the time from the start of treatment to death from any cause, is measured in months, compared to historical controls, and has an effect of 14 months.
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2024
- Study start30 Apr 2024 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GBMStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tao Sun, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06396481
- Sponsor's protocol ID
- HX-A-2022006-1
- Acronym
- CSAγδTBMG
- Status last verified
- May 2024
- First submitted
- 29 Mar 2024
- Last updated
- 2 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Allogeneic Vγ9Vδ2 T Cells in the Treatment of Brain Malignant Glioma
- ClinicalTrials.gov ID
- NCT06396481
- Acronym / sponsor ID
- CSAγδTBMG / HX-A-2022006-1
- Conditions
- GBM, DIPG Brain Tumor, Medulloblastoma
- Keywords
- malignant glioma, Vγ9Vδ2 T
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 30 Apr 2024 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 2 May 2024 (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.
Primary brain malignant tumor has become the first lethal tumor in children and young adults, and the treatment is limited, and the prognosis of patients is poor. According to the classification of the World Health Organization, glioblastoma is divided into grade II, III and IV gliomas; The higher the degree of malignancy, the worse the clinical outcome. Among them, the most malignant, most lethal, and most common types of tumors include supratentorial glioblastoma, diffuse endopontine glioma (DIPG), medulloblastoma, and ependymoma. Its high malignancy is mainly manifested in three aspects: extremely rapid growth and obvious invasion; The operation is not easy to remove all; The tumor has a tendency of recurrence and disseminated implantation. It can occur with children and adults of all ages. At present, surgery combined with chemoradiotherapy is the main treatment, but the therapeutic effect is not good. Studies have shown that glioblastoma, as the most common primary brain malignant tumor in adults, after standard surgery, radiotherapy and chemotherapy, the median survival time is less than 15 months, and the overall five-year survival rate is only 5.4%. Even after receiving new and expensive Tumor-treating fields, the median survival time is less than 21 months. The median survival time of DIPG patients is generally less than 1 year, and the 5-year survival rate is less than 5%. The average 5-year survival rate of medulloblastoma and anaplastic ependymoma is 40%~60%. Innovative treatments are urgently needed. Immunotherapy based on Vγ9Vδ2 T cells has become a promising research direction in recent years. Its unique phosphine antigen recognition does not depend on major histocompatibility complex (MHC), easy to allograft and other advantages. Making it one of the most promising cell therapies. Brain glioma has abnormal cholesterol metabolism and phosphine antigen accumulation, which is easily sensed by Vγ9Vδ2 T cells. Therefore, the clinical exploration of Vγ9Vδ2 T cells for glioma is of great significance to both the scientific and clinical communities.
Detailed description
Research purpose
- Main purpose: To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy.
- Secondary Purpose: To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma (WHO IV).
- Explore goals:
To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion. To investigate the immunological dynamics of Vγ9Vδ2 T cells after reinfusion. To explore biomarkers that might predict the clinical efficacy of Vγ9Vδ2 T cell therapy.
Research design types, principles and test steps
- Research design This is an exploratory clinical trial. It is planned to enroll 50 patients with malignant glioma (WHO Grade IV) in the Department of Neurosurgery of Beijing Tiantan Hospital to conduct a single-center, single-arm open phase I clinical trial. To evaluate the safety, feasibility, and efficacy of allogeneic Vγ9Vδ2 T cell infusion regimen in the treatment of malignant brain gliomas (WHO Grade IV). The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the cell transfusion volume was successively increased according to the doses of 1x107, 3x107, 1x108 and 3x108 per dose to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. At the same time, patients who failed to complete at least one course of precision treatment for any reason after enrollment were included in the internal control group, and patients who met the admission criteria of this study but did not participate in this study were included in the external control group, with a total of 25 cases.
- Sample size and research plan After signing the informed consent form (ICF), subjects will complete the screening period assessment according to the trial plan process sheet. Patients can be combined with the chemotherapy drug temozolomide according to the specific condition.
Recruit 20 healthy donors to provide peripheral blood. After the donors sign the informed consent, they will complete the evaluation and collection of peripheral blood according to the procedure table of the trial plan.
After screening qualified donors, it is necessary to arrange monopexing as soon as possible. The full name of mononuclear cell collection is peripheral blood mononuclear cell collection. In this study, blood cell separation will be used for mononuclear cell collection.
Monofrequency: ECG monitoring was performed before and during monofrequency, and was recorded once an hour from the beginning until the end of monofrequency. The collection time must record the circulation amount, collection volume, and collection time in a timely manner. Information on the preparation of single samples and Vγ9Vδ2 T cells was collected and recorded. If the donor does not consent to the continued use of its Vγ9Vδ2 T cells in this study, the study will be destroyed in accordance with the standard procedures prescribed by national law.
At least 15 patients with malignant brain glioma (WHO Grade IV) were initially planned to be enrolled using a staggered dosing strategy. Subject 1 and 2, and subject 2 and 3 must be monitored at least 2 weeks apart. The number of allogeneic Vγ9Vδ2 T cells was increased at each dose of 1×107, 3×107, 1×108, and 3x108 to observe their tolerance and safety. Short-term safety evaluation was performed 2-3 days after each course of cell infusion. After the treatment, according to the number of successfully prepared allogeneic Vγ9Vδ2 T cells, the study doctor can choose to continue to give cell transfusion for multiple courses according to the clinical condition of the subjects.
Further enrollment of 10 patients with malignant brain glioma (WHO Grade IV) is planned for dose-extension therapy at the optimal dose obtained above to observe tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Short-term safety evaluation was performed 2-3 days after each course of cell infusion. After the end of 3 courses, the number of successfully prepared Vγ9Vδ2 T cells can also be selected by the research doctor according to the clinical condition of the subjects to continue to give cell transfusion for multiple courses. Patients who failed to complete at least one course of precision treatment for any reason after enrollment were included in the internal control group, and patients who met the admission criteria of this study but did not participate in this study were included in the external control group, with a total of 25 cases.
Follow-up was performed at 30 days, 2 months, 3 months, 6 months, 9 months, and 12 months after the first cell reinfusion, or early withdrawal from the study, and efficacy was assessed at each follow-up.
The end of the trial was defined as withdrawal of informed consent by the last subject, termination of treatment or withdrawal from the trial, loss of follow-up or death, completion of 1 year of follow-up, or early termination of the study, whichever occurred first.
The trial may be terminated prematurely at any time for any reason attributable to the Sponsor. If necessary, the subject should have an end-of-treatment visit as soon as possible.
- Research methods Vγ9Vδ2 T cell therapy program
This is an exploratory clinical trial. It is planned to enroll 50 patients with malignant glioma (WHO Grade IV) in the Department of Neurosurgery of Beijing Tiantan Hospital to conduct a single-center, single-arm open phase I clinical trial. To evaluate the safety, feasibility, and efficacy of allogeneic Vγ9Vδ2 T cell infusion regimen in the treatment of malignant brain gliomas (WHO Grade IV).
The trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4.
The study was a single-arm, single-center intervention Phase I clinical study. The overall study was carried out in two steps:
- Uphill phase: At least 15 patients with malignant glioma (WHO Grade IV) were initially planned to be enrolled. According to the 3+3 design, the amount of cell transfusion was increased successively according to the doses of 1x107, 3x107, 1x108 and 3x108 per dose to observe the tolerance and safety of the cells.
- Expansion stage: 10 patients with malignant brain glioma (WHO Grade IV) are planned to be enrolled for dose expansion therapy according to the optimal dose obtained in the climbing stage, so as to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy. | Experimental | Biological: Vγ9Vδ2 T cellThe trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. |
| To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma | Experimental | Biological: Vγ9Vδ2 T cellThe trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. |
| To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion. | Experimental | Biological: Vγ9Vδ2 T cellThe trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with clinically diagnosed malignant brain glioma in an important structural area (WHO Grade IV);
- Patients with poor postoperative effect or ineffective guidelines for conventional treatment
- Age ≥4 years old, male or female;
- KPS score ≥70;
- Normal bone marrow reserve function and normal liver and kidney function (as evidenced by the following laboratory tests prior to initial Vγ9Vδ2 T cell therapy) :
Key exclusion criteria (16 listed)
- Pregnant and lactating women;
- Organ failure;
- Heart: Grade III and grade IV;
- Liver: Level C of the Child-Turcotte liver function scale;
- Kidney: renal failure and uremia stage;
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 |
|---|---|---|
| Vγ9Vδ2 T cellThe trial consisted of two phases: dose climbing phase and extension phase. At least 15 patients with malignant brain glioma (WHO Grade IV) were enrolled in the climbing phase. According to the 3+3 design, the amount of cells suitable for implantable Ommaya capsules for cell transfusion was increased according to the dose of 1x107, 3x107, 1x108 and 3x108 per dose, so as to observe its tolerability and safety. In the expansion phase, 10 patients with malignant brain glioma (WHO Grade IV) were enrolled, and dose expansion therapy was performed according to the optimal dose obtained in the climbing phase to observe its tolerability and safety. One course of treatment every 4 weeks, a total of 3 courses. Vγ9Vδ2 T cells were injected into the ventricle or ventricle once a week for the first three weeks and observed at the fourth week. In some patients, radiotherapy or other chemotherapy drugs (such as temozolomide) may be combined at week 4. | Biological | To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy., To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma, To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion. |
Primary outcome
Safety evaluation
Time frame: up to 12 months
The study will collect all adverse events that occurred after participants initiated leukocyte monopexy to Vγ9Vδ2 T cell therapy for a specified period of time or until disease progression. Safety assessment tests include: blood oxygen saturation should not be lower than 80mmHg; The ECG results of heart rate and ECG should be normal sinus rhythm. Blood biochemical examination of white blood cells should be maintained at 4000-10000/μL level; IL6 should be less than 200pg/mL. Safety assessment was performed according to the study protocol one day before each infusion of Vγ9Vδ2 T cells and one week after each infusion. Safety assessment tests include: blood oxygen saturation should not be lower than 80mmHg; The ECG results of heart rate, PR interval, RR interval, QRS, QT interval, QTcF and ECG should be normal sinus rhythm. Blood biochemical examination of white blood cells should be maintained at 4000-10000/μL level; IL6 should be less than 200pg/mL.
1 secondary outcome
curative effect appraising
Time frame: up to 12 months
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 2 May 2024.
- 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.
Tao Sun principal investigator
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vγ9Vδ2 T cell in people with GBM and DIPG Brain Tumor, run by Beijing Tiantan Hospital at 1 site 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 17 inclusion and 16 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: opening soon, as of the sponsor's last update on 2 May 2024. 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 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 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?
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 Tao Sun (8613331190858, suntao@bjtth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety evaluation (time frame: up to 12 months). 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 2 May 2024.