CD147-CART Cells in Patients With Recurrent Malignant Glioma.

A Clinical Study to Investigate the Safety, Tolerance and Efficacy Evaluation of Single-centre, Open-label of Local Treatment of CD147-CART in Recurrent Glioblastoma.

This is a single-center, single-arm, open label and dose escalation clinical study of anti-CD147 CART cells in patients with recurrent malignant glioma.

Study Overview

• Status: Unknown
• Conditions: Recurrent Glioblastoma; CD147 Positive
• Intervention / Treatment: Biological: CD147-CART

Detailed Description

Patients autologous T cells are activated and then engineered to express chimeric antigen receptors (CARs) specific for CD147(CD147-CART). CAR-T cells are expanded in culture and returned to the patient by Ommaya Reservoir at specific cell doses. Three CD147-CART doses patient are planned at 1-week intervals. Serum cytokine level and CAR-T cell number will be measured in whole treatment session.

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zhinan Chen, PhD; Phone Number: 029-84774547; Email: znchen@fmmu.edu.cn
• Study Contact Backup: Name: Zhou Fei, Dr; Phone Number: 029-84775323; Email: feizhou@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • National Translational Science Center for Molecular Medicine & Department of Cell Biology
      • Contact: Zhinan Chen, PhD; Email: znchen@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 year and ≤ 65 years, both male and female;
2. Recurrent glioblastoma patients confirmed by histology or cytology, which have received standard care of STUPP protocol (TMZ concurrent chemoradiotherapy and adjuvant chemotherapy protocol) after surgery;
3. Cerebral ventricle was not opened after glioma surgery;
4. More than 6 months after the first glioma surgery;
5. Tumor lesions that can be evaluated or measured according to RANO criteria (Measurable enhancement lesions were defined as enhancement lesions with clear upper boundary of CT or MRI, capable of developing on ≥2 axial films with layer thickness of 5 mm, and the length and diameter of each other were >10 mm. If the scanning layer thickness is large, the minimum measurable lesion should be >2 times thick);
6. CD147+ was confirmed by histologically diagnosis (IHC staining).
7. Adequate PBMC can be obtained according to the requirements of cell preparation, and there are no other contraindications for lymphocyte collection;
8. KPS score ≥70;
9. Patient with a life expectancy of greater than three months;
10. Patients with entirely informed consent and voluntarily sign the informed consent by themselves or their legal representative.

Exclusion Criteria:

1. Patients who have received radiotherapy after recurrence;
2. Patients who have received corticosteroids or other immunosuppressive agents in the past 2 weeks;
3. Patients who have received live vaccine in the past 4 weeks and/or plan to receive live vaccine after participating in the trial;
4. Patients who have received chemotherapy in addition to lymphocyte clearance in the past 2 weeks;
5. Patients who have not recover from adverse events caused by previous anti-tumor therapy (≤1 according to CTCAE v5.0) prior to enrollment, except for hair loss；
6. Patients who have received gene therapy, cell therapy or immune therapy；
7. Patients who have received organ transplantation；
8. Patients who cannot able to perform craniocerebral MRI examination;

9. Patients with following abnormalities:

   1. Absolute neutrophil count (ANC)<1.5×109/L， platelet (PLT)<80×109/L or hemoglobin(HGB)<100 g/dL；
   2. Prothrombin time (PT), activated partial thromboplastin time (APTT) or international normalized ratio (INR) > 1.5×ULN (upper normal value);
   3. Total bilirubin(TBIL) > 2×ULN; ALT, AST or ALP>3×ULN;
   4. Serum creatinine (Cr)≥1.5×ULN or glomerular filtration rate (GFR) < 60mL/min×1.73m2；
   5. Syphilis test (TRUST) positive, Anti-HIV positive, Anti-HCV positive with HCV-RNA level higher than the lower limit of detection (LOD), or HBcAb positive with HBV-DNA level higher than the LOD;
   6. Left ventricular ejection fraction (LVEF) < 50%;
10. An acute bacterial or fungal infection that requires intravenous antibiotics during CAR-T cell therapy;
11. Patients who presented with negligent compensatory heart failure (NYHA grade III and IV), unstable angina pectoris, acute myocardial infarction, persistent and clinically significant arrhythmia within 3 months;
12. Patients who requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks;
13. Patients with other malignant tumors that have not been effectively controlled within the past five years;
14. Patients who suffering from tuberculosis and not cured;
15. Patients with a history of allergic reactions attributed to any agents or compounds involved in this study;
16. Patients allergic to contrast agents;
17. Patients with a history of mental disorders;
18. Patients with a history of drug abuse;
19. Pregnant and lactating women, or planning to become pregnant during the study;
20. Patients of childbearing age who unwilling or unable to use effective and adequate contraception during and 3 months after the study;
21. Patients who enrolled in other clinical trials within 30 days;
22. Patients who were considered not suitable for this clinical trial by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CD147-CART; CD147-CAR modified T cells, intracavity injection, 3+3 design with de-escalation in half step, every 7 days for 3 weeks	Biological: CD147-CART; Three doses of CD147-CART cells were injection to intracavity by Ommaya Reservoir.; Other Names: anti-CD147 chimeric antigen receptor T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and type of adverse events induced by CD147-CART	To assess the safety and tolerability of CD147-CART (anti-CD147 CAR-T cell) for glioma which measured by number and type of adverse events.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT and MTD of CD147-CART cell	To determine the dose limited toxicity (DLT) and maximum tolerated dose (MTD) of CD147-CART.	12 weeks
Clinical Activity of CD147-CART cell	To evaluate treatment response of CD147-CART for glioma	2 years
CD147-CART detection in Peripheral Blood	Quantification of CD147-CART cells in blood samples.	2 years

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2019
• Primary Completion (ANTICIPATED): October 30, 2020
• Study Completion (ANTICIPATED): May 30, 2022

Study Registration Dates

• First Submitted: August 4, 2019
• First Submitted That Met QC Criteria: August 4, 2019
• First Posted (ACTUAL): August 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; glioma; CD147
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: Chen Zhinan-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No