Clinical Trials /

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

NCT03941626

Description:

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.

Related Conditions:
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Glioblastoma
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Autologous CAR-T/TCR-T Cell Immunotherapy for Solid Malignancies
  • Official Title: EGFRvIII/DR5/NY-ESO-1/Mesothelin CAR-T/TCR-T Cells Immunotherapy for Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2019BDB016
  • NCT ID: NCT03941626

Conditions

  • Esophagus Cancer
  • Hepatoma
  • Glioma
  • Gastric Cancer

Interventions

DrugSynonymsArms
CAR-T/TCR-T cells immunotherapyCAR-T/TCR-T cells immunotherapy

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
CAR-T/TCR-T cells immunotherapyExperimentalEnrolled patients will receive CAR-T cell immunotherapy with several different specific Chimeric antigen receptors aiming at different antigens respectively by infusion.
  • CAR-T/TCR-T cells immunotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must be willing to sign an informed consent.

          2. Male or female patients aged 18 to 70 years .

          3. Estimated survival of ≥ 12 weeks.

          4. 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.

          5. Solid tumor must have at least one measureable disease according to RECIST 1.1.

          6. Routine blood test#hemoglobin>=90 g/L; platelet>=50×10^9/L.

          7. 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.

          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.

         10. Cardiac function: stable hemodynamic and left ventricular ejection fraction
             (LVEF)>=55%.

         11. ECOG score:0-1.

         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. Subjects of
             reproductive potential must agree to use acceptable birth control methods within 1
             year after treatment, as described in protocol.

         14. 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:

          1. 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.

          2. EGFRvIII, the target antigen, must be identified on tumor tissue by IHC or PCR, i.e.
             EGFRvIII positive via pathology report.

          3. Insensitivity to chemoradiotherapy or chemoradiotherapy failure after operation
             molecular pathology.

          4. Refused to receive radiotherapy or chemotherapy treatment.

        Patients with liver cancer

          1. DR5 or EGFRvIII positive via pathology report.

          2. Untreatable by surgery ; Or postoperative recurrence ;Or no effective treatment.

          3. Liver function:child-pugh A grade or child-pugh B grade.

        Patients with gastric cancer

          1. Mesothelin positive via pathology report.

          2. The pathological stage:IIIA~IV.

          3. chemoradiotherapy failure

          4. Refused or unable to get surgery.

        Patients with esophageal cancer

          1. NY-ESO-1 positive via pathology report and HLA-A*0201 positive in blood.

          2. Refuse or unable to get surgery.

          3. Postoperative recurrence or chemoradiotherapy failure.

        Exclusion Criteria:

          1. ECOG≥2.

          2. malignant tumor cells with T cell origin via pathology test.

          3. Organ failure: stage III or IV congestive heart failure; Renal failure and uremia;
             respiratory failure; disturbance of consciousness.

          4. Acute or chronic GVHD after allogeneic hematopoiesis; Or being treated for GVHD; Or
             hormone or immunosuppressant used within 30 days

          5. steroid hormoneswere used before and after blood collection and infusion

          6. Patients with HIV infection or active hepatitis

          7. Uncontrolled active infection.

          8. Enrolled to other clinical study in the last 4 weeks.

          9. Patients with systemic auto-immune disease or immunodeficiency.

         10. Patients with neuropathy or psychosis, including dementia or epilepsy, or history of
             psychotropic substance abuse, or other substantial lesions that may increase central
             neurotoxicity.

         11. Concomitant with the second tumor or other malignant tumors.

         12. Patients with bone metastases are at risk of a pathological fracture resulting in
             paraplegia or life threatening.

         13. Live attenuated vaccine was administered within 4 weeks prior to blood collection.

         14. Blood oxygen saturation is maintained by oxygen inhalation.

         15. Received major surgery within 2 weeks prior to screening ;Or Plan to receive surgery
             during study or within 2 weeks after injection.

         16. Other patients that researchers considered unsuitable for inclusion.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
Time Frame:48 months
Safety Issue:
Description:Safety evaluation

Secondary Outcome Measures

Measure:Clinical response
Time Frame:48 months
Safety Issue:
Description:Clinical response to T-cell infusion, especially change of tumor volume will be evaluated by comparing disease identified by computed tomography, magnetic resonance imaging.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shenzhen BinDeBio Ltd.

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