Trial Title:
Clinical Study of Allogeneic Vγ9Vδ2 T Cells in the Treatment of Brain Malignant Glioma
NCT ID:
NCT06396481
Condition:
GBM
DIPG Brain Tumor
Medulloblastoma
Conditions: Official terms:
Glioma
Medulloblastoma
Diffuse Intrinsic Pontine Glioma
Conditions: Keywords:
malignant glioma
Vγ9Vδ2 T
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Biological
Intervention name:
Vγ9Vδ2 T cell
Description:
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.
Arm group label:
To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy.
Arm group label:
To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant glioma
Arm group label:
To investigate the expansion, infiltration and persistence of Vγ9Vδ2 T cells after reinfusion.
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.
Detailed description:
Research purpose
1. Main purpose:
To evaluate the safety and feasibility of allogeneic Vγ9Vδ2 T cell therapy.
2. Secondary Purpose:
To evaluate the therapeutic effect of allogeneic Vγ9Vδ2 T cells on brain malignant
glioma (WHO IV).
3. 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
1. 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.
2. 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.
4. 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:
1. 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.
2. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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;
- The researchers believe that other reasons are not suitable for clinical trials
Gender:
All
Minimum age:
4 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Beijing Tiantan Hospital, Capital Medical University
Address:
City:
Beijing
Zip:
100070
Country:
China
Contact:
Last name:
Tao Sun
Phone:
8613331190858
Email:
suntao@bjtth.org
Investigator:
Last name:
Tao Sun
Email:
Principal Investigator
Start date:
April 30, 2024
Completion date:
December 30, 2027
Lead sponsor:
Agency:
Beijing Tiantan Hospital
Agency class:
Other
Source:
Beijing Tiantan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06396481
