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

NCT ID: NCT05459441

Last Updated: 2022-07-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2023-12-31

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.

Conditions

Glioma; Brain Metastases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment of glioma

For patients with glioma, after the patient's general condition was stable, contraindications were excluded and RAK cells were injected into Ommaya sac.

Group Type: EXPERIMENTAL

Autologous progenitor expansion -T

Intervention Type: BIOLOGICAL

After the completion of RAK cell culture, RAK cells were slowly injected into the tumor cavity through Ommaya capsule for no less than 10 minutes, each time about 1.0-4.0 108/4 mL, once a week,3 times as a course of treatment. Il-2 (500,000 units/capsule) was injected into the tumor cavity through Ommaya reservoir every other day after the injection of RAK cells In other words, the day of RAK cell injection was the first day, and the third and fifth days were respectively injected. Then, about LML of sac fluid was pumped back before each injection to observe the growth of RAK cells in the tumor cavity. Il-2 was dissolved with LML normal saline, and the fluid storage sac was pressed 3-5 times after injection to make the sac fluid and IL-2 fully mixed.

Treatment of brain metastases

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.

Group Type: EXPERIMENTAL

Autologous progenitor expansion -T

Intervention Type: BIOLOGICAL

After the completion of RAK cell culture, RAK cells were slowly injected into the tumor cavity through Ommaya capsule for no less than 10 minutes, each time about 1.0-4.0 108/4 mL, once a week,3 times as a course of treatment. Il-2 (500,000 units/capsule) was injected into the tumor cavity through Ommaya reservoir every other day after the injection of RAK cells In other words, the day of RAK cell injection was the first day, and the third and fifth days were respectively injected. Then, about LML of sac fluid was pumped back before each injection to observe the growth of RAK cells in the tumor cavity. Il-2 was dissolved with LML normal saline, and the fluid storage sac was pressed 3-5 times after injection to make the sac fluid and IL-2 fully mixed.

pemetrexed

Intervention Type: DRUG

For patients with brain metastasis from solid tumor that met the inclusion conditions, the Ommaya capsule was placed 2 days later, and the maximum tolerated dose of pemetrexed intrathecal chemotherapy was injected intravaginally at 10mg according to the general situation of the patients and the results of the previous study.

Interventions

Autologous progenitor expansion -T

After the completion of RAK cell culture, RAK cells were slowly injected into the tumor cavity through Ommaya capsule for no less than 10 minutes, each time about 1.0-4.0 108/4 mL, once a week,3 times as a course of treatment. Il-2 (500,000 units/capsule) was injected into the tumor cavity through Ommaya reservoir every other day after the injection of RAK cells In other words, the day of RAK cell injection was the first day, and the third and fifth days were respectively injected. Then, about LML of sac fluid was pumped back before each injection to observe the growth of RAK cells in the tumor cavity. Il-2 was dissolved with LML normal saline, and the fluid storage sac was pressed 3-5 times after injection to make the sac fluid and IL-2 fully mixed.

Intervention Type: BIOLOGICAL

pemetrexed

For patients with brain metastasis from solid tumor that met the inclusion conditions, the Ommaya capsule was placed 2 days later, and the maximum tolerated dose of pemetrexed intrathecal chemotherapy was injected intravaginally at 10mg according to the general situation of the patients and the results of the previous study.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Pudong Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jun Ren, MD,PhD

Role: STUDY_CHAIR

Fudan University Pudong Medical Center

Locations

Fudan University Pudong Medical Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Ren, MD,PhD

Role: CONTACT

jun.ren@duke.edu

021-68035321

Facility Contacts

Jun Ren, MD,PhD

Role: primary

jun.ren@duke.edu

021-68035322

Other Identifiers

2022-IIT-004-F01

Identifier Type: -

Identifier Source: org_study_id