Status:
TERMINATED
Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
Lead Sponsor:
University of Pennsylvania
Collaborating Sponsors:
University of California, San Francisco
Conditions:
Patients With Residual or Reccurent EGFRvIII+ Glioma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 E...
Eligibility Criteria
Inclusion
- 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:
- Subject met all Step 1 Eligibility Criteria.
- 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.
- 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).
- If the patient is on dexamethasone, the dose must be 4 mg/day or less prior to CART-EGFRvIII infusion.
- 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.
- Life expectancy less greater than 3 months
- 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)
Exclusion
Key Trial Info
Start Date :
November 18 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 4 2018
Estimated Enrollment :
11 Patients enrolled
Trial Details
Trial ID
NCT02209376
Start Date
November 18 2014
End Date
April 4 2018
Last Update
June 22 2023
Active Locations (2)
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1
UCSF
San Francisco, California, United States
2
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104