Efficacy and Safety Evaluation of Percutaneous Ommaya Capsule Injection of Autologous Bi-dimensional Specific T Cells in the Treatment of Glioma and in Combination With Pemetrexed in the Treatment of Brain/Meningeal Metastases

Early Phase 1

• Conditions: Glioma; Brain Metastases
• Interventions: Biological: Autologous progenitor expansion -T; Drug: pemetrexed

• Registration Number: NCT05459441
• Lead Sponsor: Shanghai Pudong Hospital

Brief Summary

Cerebral metastases are common intracranial tumor, its incidence increased year by year, in recent years, although the whole brain radiation therapy, surgical resection, stereotactic radiosurgery treatment, targeted drugs, and other comprehensive treatment in patients with symptoms of mitigation and the extension of survival has played a positive role, but due to individual differences, treatment in patients with poor compliance were a lot of factors, Further treatment of brain metastases after conventional treatment requires the assistance and cooperation of clinical multi-disciplines. To evaluate the efficacy and safety of percutaneous Ommaya capsule injection of autologous bi-dimensional specific T cells in the treatment of glioma and combined with pemetrexed in the treatment of brain/meningeal metastasis. Using translational research techniques and means, to find molecular indicators related to clinical prognosis and outcome, establish the clinical use standard of this holistic treatment technology, and popularize it in multi-centers.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-01
• Status Verified: 2022-02
• Study First Submitted: 2022-06-24
• Study First Submitted QC: 2022-07-12
• Last Update Submitted: 2022-07-12
• Study First Posted: 2022-07-15
• Last Update Posted: 2022-07-15
• Primary Completion: 2023-06-30
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Clear diagnosis of glioma; The pathological diagnosis of the primary lesion is clear, and the intracranial lesion can be diagnosed as intracranial metastasis by clinical, cerebrospinal fluid and imaging diagnosis according to the standards of the European Society of Neuro-Oncology - European Society of Medical Oncology (EANo-ESMO).

2. Patients with glioma and solid tumor with brain metastasis who have relapsed after surgery, whole brain radiotherapy or chemotherapy, or who are intolerant and not suitable for surgery or radiotherapy, and who are determined by clinicians to no longer benefit from systemic chemotherapy;

3. Surgical indications for Ommaya capsule implantation;

4. Age ≥18 years old and ≤80 years old, regardless of gender;

5. ECOG score for general physical condition is 0 ~ 2;

6. The expected survival time is at least 1 month;

7. WBC≥3.0×109/L, Hb≥90g/L, PLT≥75×109/L at baseline upon enrollment;

8. Liver and kidney function are basically normal A) Liver: total bilirubin ≤2.0 mg/dL (34.2umol/L), AST and ALT≤ 2.5 times the upper limit of normal value, AST and ALT≤ 5 times the upper limit of normal value in patients with liver metastasis.

   B) Kidney: creatinine ≤2.5 mg/dL (221umol/L), creatinine clearance ≥60 mL/min;

9. Understand and sign informed consent to participate in clinical study voluntarily.

Exclusion Criteria

1. Patients with primary brain tumors other than glioma;
2. Patients with systemic metastasis, poor general condition, and expected survival time less than 1 month;
3. People allergic to pemetrexed;
4. Severe coagulation disorder;
5. Severe active infection and other serious complications;
6. Patients with active viral hepatitis;
7. There are urgent intracranial symptoms (cerebral hernia, etc.), systemic diseases affecting treatment, and basic diseases affecting patients' cognitive function (such as cerebrovascular diseases, Alzheimer's disease, etc.);
8. Pregnant or lactating women;
9. Within 4 weeks prior to enrollment, translumbar administration was performed;
10. Other factors considered by researchers are not suitable candidates.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment of glioma	Autologous progenitor expansion -T	For patients with glioma, after the patient's general condition was stable, contraindications were excluded and RAK cells were injected into Ommaya sac.
Treatment of brain metastases	Autologous progenitor expansion -T	For patients with brain/meninges metastasis, Ommaya capsule was placed subcutaneously after puncture under local anesthesia. Two days after surgery, chemotherapy was started when the intracranial pressure was stable and the condition was stable, and the conjunctivitis was eliminated. Intracapsular injection of autoimmune cells was started in the second week after chemotherapy.
Treatment of brain metastases	pemetrexed	For patients with brain/meninges metastasis, Ommaya capsule was placed subcutaneously after puncture under local anesthesia. Two days after surgery, chemotherapy was started when the intracranial pressure was stable and the condition was stable, and the conjunctivitis was eliminated. Intracapsular injection of autoimmune cells was started in the second week after chemotherapy.

Primary Outcome Measures

Name	Time	Method
Clinical response rate	24 months	The percentage of patients with CR and PR in the total number of patients in the same period

Secondary Outcome Measures

Name	Time	Method
Safty(adverse events)	12 months	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Overall survival (OS)	24 months	Frome the starting date of the enrollment until the date of the first documented disease progression or the date of the death from any cause,whichever comes first

Trial Locations

Locations (1)

Fudan University Pudong Medical Center; 🇨🇳 Shanghai, Shanghai, China