Anti-GPC3 CAR T for Treating Patients With Advanced HCC
The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize glypican-3 (GPC3) is safe and effective for patients with relapsed or refractory hepatocellular carcinoma (HCC).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Autologous T Cells Redirected to GPC3 for Treating Patients With Advanced HCC|
Primary Outcome Measures:
- Adverse events attributed to the administration of the anti-GPC3 CAR T cells [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
|Ages Eligible for Study:||18 Years to 70 Years|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
- Patients with HCC must be greater than or equal to 18 years of age and less than or equal to age 70, and must have a life expectancy > 12 weeks
- GPC3 is expressed in HCC tissues by IHC.
- Non-diffuse HCC with the presence of extrahepatic metastasis or portal vein vascular invasion.
- The liver cirrhosis status should be Child-Pugh A or B with a score equal to 7.
- ECOG physical status score is equal to 0-1 or KPS score is higher than 80.
- Enough venous access for apheresis or venous sampling and no contraindications to other blood cell separation
- WBC≥2500/ml，PLT≥60×10^9 /L，Hb≥9.0g/dL，LY≥0.7×10^9/L，LY%≥15%，Alb≥2.8g/dL， serum lipase and amylase＜1.5 ULN，serum creatinine≤2.5mg/dL，ALT and AST≤5 ULN，serum total bilirubin≤3.0mg/dL，PT:INR＜1.7 or PT beyond the normal value less than 4s.
All laboratory test results should be in the stable range, and no persistent support treatment is given.
- The transduction efficiency of the T cells is less than 30% or the amplification of the T cells via αCD3/CD28 stimulation is less than 5 times.
- Pregnant or lactating women (the safety of the experimental treatment to the unborn baby is unknown; The pregnancy status of the female participants should be negative when her serum or urine is evaluated 48 hrs before infusion).
- Active systemic infections, coagulation disorders or other major medical illnesses including those of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
- Steroid is now systemically used.
- Prior treatment with any other gene therapeutics.
- the past or present existence of hepatic encephalopathy
- The existence of unstable or active ulcers or gastrointestinal bleeding
- Patients with a history of organ transplantation or are waiting for organ transplantation.
- serum sodium＜125mmol/L
- baseline serum K＜3.5mmol/L（The patients can be included when the serum K≧3.5mmol/L after supplementation）
- patients need anticoagulant therapy (such as warfarin or heparin)
- patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d)
- Patients treated by radiotherapy within 4 weeks prior the first apheresis.
- Patients using fludarabine or cladribine chemotherapy within two years
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.Please refer to this study by its ClinicalTrials.gov identifier: NCT02395250
|Contact: Zonghai Li, MDemail@example.com|
|Shanghai Cancer Institute||Recruiting|
|Xuhui, Shanghai, China, 200032|
|Contact: zonghai li, MD 86-21-64436601 firstname.lastname@example.org|
|Principal Investigator: Zonghai Li, MD|
|Study Director:||Bo Zhai, MD||Renji|
No publications provided
|Responsible Party:||RenJi Hospital|
|ClinicalTrials.gov Identifier:||NCT02395250 History of Changes|
|Other Study ID Numbers:||RJ-20150313|
|Study First Received:||March 17, 2015|
|Last Updated:||March 17, 2015|
|Health Authority:||China: Ethics Committee|
Additional relevant MeSH terms:
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial