Patients With Residual or Reccurent EGFRvIII+ Glioma Clinical Trial
Official title:
Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
| Verified date | March 2019 |
| Source | University of Pennsylvania |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 11 |
| Est. completion date | April 4, 2018 |
| Est. primary completion date | April 4, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| United States | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | UCSF | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| University of Pennsylvania | University of California, San Francisco |
United States,
O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey SF, Navenot JM, Zheng Z, Levine BL, Okada H, June CH, Brogdon JL, Maus MV. A single dose of peri — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of adverse events | 2 years |