Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM (INTERCEPT)

This is an interventional treatment trial for Recurrent Glioblastoma focused on measuring Malignant Glioma, INTERCEPT, Pro00083828, Adult, Chimeric Antigen Receptor, CAR T cell, EGFRvIII Read More

Inclusion Criteria:

1. Disease progression or recurrence of a supratentorial World Health Organization (WHO) grade IV malignant glioma (GBM or gliosarcoma) based on imaging studies with measurable disease. At the time of biopsy, prior to stereotactic radiosurgery (SRS) and administration of the EGFRvIII-CARS, the presence of recurrent tumor must be confirmed by histopathological analysis.
2. Adults ≥ 18 years old.
3. Karnofsky Performance Status (KPS) score ≥ 70.
4. EGFRvIII, the target antigen, must be identified on tumor tissue by immunohistochemistry (IHC) or Polymerase Chain Reaction (PCR), i.e. EGFRvIII positive via pathology report.
5. Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥ 125,000 cells/µl (prior to biopsy).
6. Serum creatinine ≤ 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT), and bilirubin ≤ 1.5 times upper limit of normal (prior to biopsy).
7. Signed informed consent approved by the Institutional Review Board.
8. Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [IUD; only hormonal], sexual abstinence or vasectomized partner) during the trial and for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 48 hours prior to starting SRS.
9. Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, IUDs [only hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of > 6 months following the last administration of trial drugs.
10. Meet eligibility requirements for SRS: able to get MRI; the patient must have a lesion that, in the opinion of the study radiation oncologist, can safely receive SRS to the entire tumor; must not be abutting optic apparatus or brainstem and catheter tip will be at least 5mm away from the ventricle; and must be able to be secured and positioned in a stereotactic U-frame mask.

Exclusion Criteria:

1. Pregnant or breast-feeding.
2. Patients with known potentially anaphylactic allergic reactions to gadolinium-DTPA.
3. Patients who cannot undergo MRI with contrast or SPECT/CT.
4. Patients with evidence of tumor in the brainstem, cerebellum, optic apparatus, or spinal cord, radiological evidence of actively growing multifocal disease, or leptomeningeal disease.
5. Patients < 12 weeks from the end of radiation therapy, unless they have two progressive scans at least 4 weeks apart, have progression outside of the radiation field, or have histologic confirmation of progression.

6. Severe, active comorbidity, including any of the following:

   1. Unstable angina and/or congestive heart failure requiring hospitalization;
   2. Transmural myocardial infarction within the last 6 months;
   3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation;
   4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy;
   5. Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
   6. Known autoimmune disorder, such as HIV;
   7. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy;
   8. Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity.
7. Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
8. Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
9. Current, recent (within 4 weeks of the administration of this study agent), or planned participation in another experimental therapeutic drug study.
10. Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)] prior to biopsy unless patients have recovered from side effects of such therapy.
11. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5 F, 37.5 C).
12. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to CAR T Cell infusion.
13. Prior therapy targeted to EGFRvIII.
14. Prior history of brain SRS, (patients who have received external beam radiation per standard of care are allowed).