Clinical Study of Allogeneic Vγ9Vδ2 T Cells in the Treatment of Brain Malignant Glioma

NCT06396481 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: HX-A-2022006-1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

GBM; DIPG Brain Tumor; Medulloblastoma

Keywords

malignant glioma; Vγ9Vδ2 T

Outcome Measures

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.

  up to 12 months

Secondary Outcomes (1)

• curative effect appraising

  up to 12 months

Study Arms (3)

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.

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.

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.

Biological: Vγ9Vδ2 T cell

Interventions

Vγ9Vδ2 T cell BIOLOGICAL

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.

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.

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Medulloblastoma; Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive

Study Officials

• Tao Sun

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao Sun

CONTACT

8613331190858; suntao@bjtth.org

Yi Wang

CONTACT

8615510283250; wydeqingsu@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: May 2, 2024
• Study Start: April 30, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 2, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)