Autologous CAR-T/TCR-T Cell Immunotherapy for Solid Malignancies
Study Details
Study Description
Brief Summary
This is a single arm, open-label, uni-center, phase I-II study to evaluate the safety and effectiveness of CAR-T/TCR-T cell immunotherapy in treating with different malignancies patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The study is a multi-target gene-modified immunotherapy. CAR-T/TCR-T cells include four different tumor-specific antibody.They are as following:anti-NY-ESO-1 antibody foresophagus cancer;anti-DR5 antibody for hepatoma;;anti-EGFR vIII antibody for hepatoma and glioma;anti-Mesothelin antibody for gastric cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CAR-T/TCR-T cells immunotherapy Enrolled patients will receive CAR-T cell immunotherapy with several different specific Chimeric antigen receptors aiming at different antigens respectively by infusion. |
Biological: CAR-T/TCR-T cells immunotherapy
According to tumor burden and other conditions, patients will be treated with cyclophosphamide or fludarabine,then,CAR-T cells will be infused 48-72 hours later.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0 [48 months]
Safety evaluation
Secondary Outcome Measures
- Clinical response [48 months]
Clinical response to T-cell infusion, especially change of tumor volume will be evaluated by comparing disease identified by computed tomography, magnetic resonance imaging.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients must be willing to sign an informed consent.
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Male or female patients aged 18 to 70 years .
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Estimated survival of ≥ 12 weeks.
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Pathological sections with positive expression of NY-ESO-1, Mesothelin, EGFRvIII and DR5 was confirmed by biopsy IHC test within 12 months.If NY-ESO-1 is positive expression ,positive HLAA*0201 is required at the same time.
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Solid tumor must have at least one measureable disease according to RECIST 1.1.
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Routine blood test#hemoglobin>=90 g/L; platelet>=50×10^9/L.
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Liver function:ALT and AST≤2.5 times upper limits of normal (If the tumor infiltration is the main cause of abnormal liver function ,ALT and AST≤5 times upper limits of normal); bilirubin<2.0 mg/dL.
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Renal function:BUN: 9-20mg / dl; serum creatinine≤ 1.5 times upper limits of normal; endogenous creatinine clearance rate≥50 ml/min .
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Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV.
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Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)>=55%.
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ECOG score:0-1.
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Adequate venous access for apheresis, and no other contraindications for leukapheresis .
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Women of child-bearing age must have evidence of negative pregnancy test. Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
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Subjects with hypertension/diabetes must be stable blood pressure/blood glucose or ≤CTCAE 1 level 2 weeks before the screening.
In addition to the above criteria for inclusion, the following criteria shall be met according to the indications:
Patients with glioblastoma：
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First disease progression or disease recurrence (≥ 1 cm and ≤ 5 cm) of a supratentorial WHO grade IV malignant glioma (GBM or gliosarcoma) based on imaging studies with measurable disease.
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EGFRvIII, the target antigen, must be identified on tumor tissue by IHC or PCR, i.e. EGFRvIII positive via pathology report.
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Insensitivity to chemoradiotherapy or chemoradiotherapy failure after operation molecular pathology.
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Refused to receive radiotherapy or chemotherapy treatment.
Patients with liver cancer
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DR5 or EGFRvIII positive via pathology report.
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Untreatable by surgery ; Or postoperative recurrence ;Or no effective treatment.
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Liver function：child-pugh A grade or child-pugh B grade.
Patients with gastric cancer
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Mesothelin positive via pathology report.
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The pathological stage：IIIA～IV.
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chemoradiotherapy failure
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Refused or unable to get surgery.
Patients with esophageal cancer
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NY-ESO-1 positive via pathology report and HLA-A*0201 positive in blood.
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Refuse or unable to get surgery.
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Postoperative recurrence or chemoradiotherapy failure.
Exclusion Criteria:
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ECOG≥2.
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malignant tumor cells with T cell origin via pathology test.
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Organ failure: stage III or IV congestive heart failure; Renal failure and uremia; respiratory failure; disturbance of consciousness.
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Acute or chronic GVHD after allogeneic hematopoiesis; Or being treated for GVHD; Or hormone or immunosuppressant used within 30 days
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steroid hormoneswere used before and after blood collection and infusion
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Patients with HIV infection or active hepatitis
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Uncontrolled active infection.
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Enrolled to other clinical study in the last 4 weeks.
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Patients with systemic auto-immune disease or immunodeficiency.
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Patients with neuropathy or psychosis, including dementia or epilepsy, or history of psychotropic substance abuse, or other substantial lesions that may increase central neurotoxicity.
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Concomitant with the second tumor or other malignant tumors.
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Patients with bone metastases are at risk of a pathological fracture resulting in paraplegia or life threatening.
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Live attenuated vaccine was administered within 4 weeks prior to blood collection.
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Blood oxygen saturation is maintained by oxygen inhalation.
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Received major surgery within 2 weeks prior to screening ;Or Plan to receive surgery during study or within 2 weeks after injection.
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Other patients that researchers considered unsuitable for inclusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henan Provincial People's Hospital | Zhengzhou | Henan | China | 450052 |
Sponsors and Collaborators
- Shenzhen BinDeBio Ltd.
- Henan Provincial People's Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019BDB016