Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies

Sponsor

Shenzhen BinDeBio Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03638206

Collaborator

The First Affiliated Hospital of Zhengzhou University (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

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
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	Biological: CAR-T cell immunotherapy	Phase 1/Phase 2

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

Anticipated Enrollment :

73 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Autologous Immunotherapy With Multi-target Gene-modified CAR-T/TCR-T Cell for Malignancies

Actual Study Start Date :

Mar 1, 2018

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: CAR-T cell 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.

Arm

Intervention/Treatment

Experimental: 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.

Biological: CAR-T cell 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 [60 months]
Safety evaluation

Secondary Outcome Measures

Clinical response [60 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.
CAR-T cells testing [60 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.