Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Susan Chang

Description

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.

Official Title

Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma

Keywords

Patients With Residual or Reccurent EGFRvIII+ Glioma Glioblastoma CART-EGFRvIII T cells

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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/mm3; platelets greater than or equal to 100,000/mm3, 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:
  4. Cohort 1: Patients with first relapse of previously diagnosed primary glioblastoma. Recurrence may be determined by imaging and clinical criteria alone.
  5. Cohort 2: Patients with newly diagnosed glioblastoma with a less than 95%resection or greater than or equal to 1 cm3 of residual disease on the post-operative MRI (typically post-operative day 1).

  6. If the patient is on dexamethasone, the dose must be 4 mg/day or less prior to CART-EGFRvIII infusion.
  7. 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.
  8. Life expectancy less greater than 3 months
  9. ECOG performance status of 0 or 1
  10. Participants with adequate organ function as measured by:
  11. White blood count greater than or equal to 2500/mm3; platelets greater than or equal to 100,000/mm3, hemoglobin greater than or equal to 9.0 g/dL; without transfusion or growth factor support

  12. 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
  13. Serum creatinine less than or equal to 1.5 x upper limit of normal
  14. Coagulation tests PT and PTT have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
  15. 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.

You CAN'T join if...

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)
  • 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)

Locations

  • UCSF
    San Francisco California United States
  • Abramson Cancer Center of the University of Pennsylvania
    Philadelphia Pennsylvania 19104 United States

Lead Scientist

  • Susan Chang
    Professor, Neurological Surgery. Authored (or co-authored) 193 research publications

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of Pennsylvania
ID
NCT02209376
Study Type
Interventional
Last Updated