autologous t cells redirected to egfrviii-with a chimeric antigen receptor in patients with egfrviii+ glioblastoma

Conditions: Patients With Residual or Reccurent EGFRvIII+ Glioma

Summary: an open-label phase 1 pilot study to determine the safety and feasibility of cart-egfrviii (autologous t cells transduced with a lentiviral vector to express a chimeric antigen receptor specific for egfrviii) in the treatment of patients with egfrviii+ glioblastoma who have had their first recurrence as determined by standard imaging or have have residual disease after initial resection.


Eligibility criteria:
inclusion criteria: * pathological criteria: glioblastoma (gbm) that is histologically confirmed by pathology review of surgically resected tissue. * tumor cells from resected tissue must be available for egfrviii testing. patients who have previously been treated with an egfrviii-targeted therapy and recurred, must have a tumor sample obtained after their recurrence available for egfrviii testing. * age greater than 18 years. * if the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis. * ecog performance status of 0 or 1 documented negative serum hcg for female patients of child-bearing potential. * participants with adequate organ function as measured by: * white blood count greater than or equal to 2500/mm\^3; platelets greater than or equal to 100,000/mm\^3, hemoglobin greater than or equal to 9.0 g/dl; without transfusion or growth factor support * ast, alt, ggt, ldh, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dl * serum creatinine less than or equal to 1.5 x upper limit of normal * coagulation tests pt and ptt have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis. * provide voluntary informed consent for tissue screening and apheresis inclusion criteria step 2: 1. subject met all step 1 eligibility criteria. 2. tumor cells test positive for egfrviii expression (by rt-pcr, next generation sequencing, or immunohistochemistry) and a cart egfrviii product has been manufactured and formulated. patients who have previously been treated with an egfrviii-targeted therapy and recurred are only eligible if a tumor sample obtained after their recurrence tests positive for egfrviii. 3. stage of disease: * cohort 1: patients with first relapse of previously diagnosed primary glioblastoma. recurrence may be determined by imaging and clinical criteria alone. * cohort 2: patients with newly diagnosed glioblastoma with a less than 95% resection or greater than or equal to 1 cm\^3 of residual disease on the post-operative mri (typically post-operative day 1). 4. if the patient is on dexamethasone, the dose must be 4 mg/day or less prior to cart-egfrviii infusion. 5. it is anticipated that all patients in cohort 2 will have completed standard of care external beam radiotherapy and chemotherapy with temozolomide (tmz) at the time of the pre-infusion safety visit. 6. life expectancy less greater than 3 months 7. ecog performance status of 0 or 1 9. participants with adequate organ function as measured by: * white blood count greater than or equal to 2500/mm\^3; platelets greater than or equal to 100,000/mm\^3, hemoglobin greater than or equal to 9.0 g/dl; without transfusion or growth factor support * ast, alt, ggt, ldh, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dl * serum creatinine less than or equal to 1.5 x upper limit of normal * coagulation tests pt and ptt have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis. * adequate cardiac function (greater than ef 55%) 10. provide voluntary informed consent for study treatment. 11. female subjects of reproductive potential must agree to use a reliable method of contraception. exclusion criteria step 1: * female subjects of reproductive potential who are pregnant or lactating. female study participants of reproductive potential must have a negative serum pregnancy test as part of step 1 eligibility confirmation. * uncontrolled active infection. * active or latent chronic hepatitis b \[detectable hepatitis b surface antigen (hbsag)\] or active hepatitis c (positive serology \[hcv ab\]) infection. * hiv infection. * previous treatment with any gene therapy products. * known addiction to alcohol or illicit drugs. * history of allergy or hypersensitivity to study product excipients (human serum albumin, dmso, and dextran 40) exclusion criteria step 2: * female subjects of reproductive potential who are pregnant or lactating. female study participants of reproductive potential must have a negative serum pregnancy test within two weeks prior to cart-egfrviii cell infusion. the safety of this therapy on unborn children is not known. * uncontrolled active infection. * use of immunosuppressive agents such as cyclosporine, mmf, tacrolimus, or rapamycin within 4 weeks of enrollment on step 2. * a minimal dose of corticosteroid (dexamethasone up to 4 mg/day) is permitted. recent or current use of inhaled steroids is not exclusionary. * previous treatment with any gene therapy products. * subjects or their physicians anticipate use of any of the following concurrent treatment or medications including: a. radiosurgery (except for the standard of care fractionated external radiation therapy is a part of the protocol regimen in cohort 2) b. chemotherapy (except for the standard of care temozolomide therapy in cohort 2) c. interferon (e.g. intron-a®) d. allergy desensitization injections e. any ongoing investigational therapeutic medication. f. bevacizumab * participants who have another cancer diagnosis with history of visceral metastases at the time of pre-entry evaluation. the following diagnoses are examples that will be allowed: * squamous cell cancer of the skin without known metastasis * basal cell cancer of the skin without known metastasis * carcinoma in situ of the breast (dcis or lcis) * carcinoma in situ of the cervix * prostate cancer with only psa recurrence * any cancer that has not required systemic therapy (other than hormonal therapies) for the past three (3) years. * any uncontrolled active medical disorder that would preclude participation as outlined. * unstable angina and/or myocardial infarction within 6 months prior to screening * known addiction to alcohol or illicit drugs. * history of allergy or hypersensitivity to study product excipients (human serum albumin, dmso, and dextran 40)