Autologous Immunotherapy With Multi-target Gene-modified CAR-T/TCR-T Cell for Malignancies
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
Study Overview
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.
Detailed Description
The study is a multi-target gene-modified immunotherapy. CAR-T/TCR-T cells include ten different tumor-specific antibody.They are as following:anti-CD19 antibody for B cell leukemia and lymphoma;anti-CD22 antibody for B cell leukemia and lymphoma;anti-CD33 antibody for myeloid leukemia;anti-BCMA antibody for multiple myeloma;anti-CD38 antibody for multiple myeloma;anti-NY-ESO-1 antibody for multiple myeloma,esophagus cancer,lung cancer,melanoma and synovial sarcoma;anti-DR5 antibody for hepatoma;anti-C-met antibody for hepatoma,colorectal cancer,ovarian cancer and renal carcinoma;anti-EGFR V III antibody for hepatoma,lung cancer and glioma;anti-Mesothelin antibody for gastric cancer,pancreatic cancer and mesothelioma.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 4 Years to 70 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •If patients had receive immunotherapy, they should reach PR/NR, or recurrency.
- •Patients must be willing to sign an informed consent.
- •age: 4 to 70 years
- •Estimated survival of ≥ 12 weeks, but ≤ 2 years
- •Blood tumor or solid tumor was diagnosed by histopathology.Positive expression of CD19, CD22, CD33, CD38, BCMA, NY-ESO-1, c-met, Mesothelin, CEGFRvIII and DR5 was confirmed by biopsy IHC test or flow cytometry test. If NY-ESO-1 is positive expression ,positive HLA-A*0201 is required at the same time .
- •Subjects with solid tumor must have measureable disease
- •Routine blood test：hemoglobin>=90 g/L; platelet>=50×10^9/L.
- •Renal function:BUN: 9-20mg / dl; serum creatinine<= 1.5 times upper limits of normal; endogenous creatinine clearance rate>=50 ml/min
- •Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV(patients with liver cancer were excluded)
- •Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)>=55%.
- •ECOG score ≤2
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis
- •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.
Exclusion Criteria
- •Patients with history of T cell tumors
- •Patients with severe insufficient cardiac, pulmonary and hepatorenal functions
- •Acute or chronic GVHD after allogeneic hematopoiesis
- •steroid hormoneswere used before and after blood collection and infusion
- •HIV infection or active hepatitis B or hepatitis C infection
- •Uncontrolled active infection
- •Enrolled to other clinical study in the last 4 weeks.
- •Subjects with systemic auto-immune disease or immunodeficiency.
- •Subjects with CNS diseases.
- •Other patients that researchers considered unsuitable for inclusion
Arms & Interventions
CAR-T cell immunotherapy
Enrolled patients will receive CAR-T cell immunotherapy with several different specific Chimeric antigen receptors aiming at different antigens respectively by infusion.
Intervention: CAR-T cell immunotherapy (Biological)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
Time Frame: 60 months
Safety evaluation
Secondary Outcomes
- Clinical response(60 months)
- CAR-T cells testing(60 months)