Clinical Study of Allogeneic Vγ9Vδ2 T Cells in the Treatment of Brain Malignant Glioma
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age4+
SponsorBeijing Tiantan Hospital
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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;
Disqualifiers
Pregnant and lactating women;
Organ failure;
Heart: Grade III and grade IV;
Liver: Level C of the Child-Turcotte liver function scale;
Trial design
Design model
Parallel
Treatments tested in this trial
Vγ9Vδ2 T cell
Biological/VaccineThe 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.
Treatment groups
25 Participants
are divided into 3 treatment groupsGroup A: To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy.Experimental treatment 1 intervention
Group B: To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant gliomaExperimental treatment 1 intervention
Group C: To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion.Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
up to 12 monthsSecondary 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.
Time frame
up to 12 monthsSponsors and contacts
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Source ClinicalTrials.gov
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