Clinical trial NCT03638206: Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
Official title: Autologous Immunotherapy With Multi-target Gene-modified CAR-T/TCR-T Cell for Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Lymphoma
Myeloid Leukemia
Multiple Myeloma
Hepatoma
Gastric Cancer
Pancreatic Cancer
Mesothelioma
Colorectal Cancer
Esophagus Cancer
Lung Cancer
Glioma
Melanoma
Synovial Sarcoma
Ovarian Cancer
Renal Carcinoma
Lead sponsor: Shenzhen BinDeBio Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
First posted: 2018-08-20
Enrollment: 73
Sex: ALL
Minimum age (years): 4
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. If patients had receive immunotherapy, they should reach PR/NR, or recurrency.
2. Patients must be willing to sign an informed consent.
3. age: 4 to 70 years
4. Estimated survival of ≥ 12 weeks, but ≤ 2 years
5. 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 .
6. Subjects with solid tumor must have measureable disease
7. Routine blood test：hemoglobin\>=90 g/L; platelet\>=50×10\^9/L.
8. Renal function:BUN: 9-20mg / dl; serum creatinine\<= 1.5 times upper limits of normal; endogenous creatinine clearance rate\>=50 ml/min
9. Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV(patients with liver cancer were excluded)
10. Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)\>=55%.
11. ECOG score ≤2
12. Adequate venous access for apheresis, and no other contraindications for leukapheresis
13. Women of child-bearing age must have evidence of negative pregnancy test.
14. Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.

Exclusion Criteria:

1. ECOG \>= 3
2. Patients with history of T cell tumors
3. Patients with severe insufficient cardiac, pulmonary and hepatorenal functions
4. Acute or chronic GVHD after allogeneic hematopoiesis
5. steroid hormoneswere used before and after blood collection and infusion
6. HIV infection or active hepatitis B or hepatitis C infection
7. Uncontrolled active infection
8. Enrolled to other clinical study in the last 4 weeks.
9. Subjects with systemic auto-immune disease or immunodeficiency.
10. Subjects with CNS diseases.
11. Other patients that researchers considered unsuitable for inclusion

Primary outcomes:
measure: Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
timeFrame: 60 months
Secondary outcomes:
measure: Clinical response
timeFrame: 60 months
measure: CAR-T cells testing
timeFrame: 60 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
References: