CAR-T Cell Immunotherapy for HCC Targeting GPC3

CAR-T Cell Immunotherapy Clinical Trial

Official title:

Chimeric Antigen Receptor-Modified T Cell (CAR-T) Immunotherapy for Hepatocellular Carcinoma (HCC) Targeting Glypican-3 (GPC3)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02723942
• Other study ID #: CAR-T for GPC3+ HCC
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: June 2015
• Est. completion date: August 15, 2016

Study information

• Verified date: July 2020
• Source: Fuda Cancer Hospital, Guangzhou
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to preliminarily evaluate the safety and efficacy of CAR-T cell immunotherapy for GPC3 positive hepatocellular carcinoma.

Description:

Chimeric antigen receptor (CAR) is a recombinant receptor with both antigen-binding and T cell activating functions. Chimeric antigen receptor T cell Immunotherapy has more advantages compared with conventional immunotherapy, especially in dealing with patients of hematologic malignancies and solid malignant tumors.This study design a novel specific Chimeric antigen receptor targeting glypican-3(GPC3) antigen.After CAR-T cell infusion,At periodic intervals, the investigators will evaluate clinical symptoms Improved conditions of this disease.Through this study,the investigators will evaluate the safety and efficacy of CAR-T cell immunotherapy in treating with GPC3 positive malignant glioma patients.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 15, 2016
• Est. primary completion date: August 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age:18-70 years.

2. Gender:both.

3. GPC3 high expression hepatocellular carcinoma patients.

4. Non diffuse hepatocellular carcinoma,no extrahepatic metastasis or portal vein vascular invasion.

5. Degree of liver cirrhosis:class A or class B 7 according to Child-puge grading standard.

6. Routine blood test:white blood cell count(WBC)>=3×10^9/L, Lymphocyte percentage>=15%, hemoglobinHbo(Hb)>=90g/L, prothrombin time(PT) prolongation<=50% normal value, Cluster of differentiation 3(CD3) positive T cell count>=0.8×10^9/L.

7. Liver and Pancreatic function:Alanine aminotransferase/Aspartate transaminase(ALT/AST)<=5 times of the normal value, total bilirubin(TBiL)<=3.0mg/dL, albumin(ALB)>=35g/L, prothrombin time(PT):International Normalized Ratio(INR)<=1.7 or prothrombin time(PT) prolongation<=4s, Serum lipase<=1.5 times of the normal value, Serum amylase<=1.5 times of the normal value.

8. Renal function:Serum creatinine(SCr)<=221µmol/L(2.5mg/L).

9. Karnofsky Performance Status(KPS)>=60;Expected survival time>=12 weeks.

10. Peripheral venous access ;no contraindication of lymphocyte separation.

11. No other serious complications.

12. Voluntarily signed informed consent.

Exclusion Criteria:

1. Pregnant and lactating women.

2. Lymphocyte separation or peripheral venous access cannot be performed in patients .

3. Patients in the active stage of infection or with coagulation disorders.

4. Patients with a previous history of hepatic coma.

5. Patients with severe gastrointestinal ulcers or gastrointestinal bleeding.

6. Patients with organ transplantation or waiting for organ transplantation.

7. Patients with anticoagulant therapy.

8. Patients with antiplatelet therapy.

9. Serum sodium(Na)<125 mmol/L.

10. Serum potassium(K)<3.5 mmol/L(except patients up to the standards after the use of supplements).

11. Patients with organ failure:

1. cardiac function:level three or above according to New York Heart Association (NYHA) criteria.

2. liver function:class C or above according to Child-puge grading standard.

3. renal function:Chronic kidney disease(CKD) phase 4 or more; renal insufficiency phase ? or more.

4. pulmonary function:severe respiratory failure symptoms, involving other organs.

5. Brain function:central nervous system abnormalities or disturbance of consciousness.

12. Patients with non controlled infectious diseases,for example,HIV positive, syphilis, hepatitis A, hepatitis B, hepatitis C, hepatitis E virus (HEV) positive etc.

13. Patients used corticosteroids or other immunosuppressive agents in the past 4 weeks.

14. Patients with autoimmune disease.

15. Patients with previous history of gene therapy.

16. The actual transfection rate of T cells was lower than 30% or the proliferation was less than 5 times after costimulation.

17. Patients participated in other drug trials in the past 4 weeks.

18. Patients received radiation treatment in the past 4 weeks.

19. Patients do not meet the criteria above.

Related Conditions & MeSH terms

• CAR-T Cell Immunotherapy
• Carcinoma
• Carcinoma, Hepatocellular
• GPC3 Positive Hepatocellular Carcinoma

Intervention

Biological:
• CAR-T cell immunotherapy
This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen.

Locations

Country	Name	City	State
China	Central laboratory in Fuda cancer hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Fuda Cancer Hospital, Guangzhou

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiological assessment	Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan.	3 months
Secondary	The safety of CAR-T cell immunotherapy (adverse events)	After CAR-T cell infusion,we will observe the potential adverse events related to the T-cell infusion such as high fever,jaundice, kidney failure and so on.	4 weeks
Secondary	Peripheral blood tumor markers	tested regularly to reflect the role of the Chimeric Antigen Receptor-Modified T Cell in the removal of residual tumor cells.	3 months
Secondary	CAR-T cell testing	The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival.	3 months