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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT02209376
First received: August 4, 2014
Last updated: January 25, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention
Patients With Residual or Reccurent EGFRvIII+ Glioma Biological: CART-EGFRvIII T cells

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: 2 years ]

Estimated Enrollment: 12
Study Start Date: July 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Biological: CART-EGFRvIII T cells

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02209376

Locations
United States, California
UCSF
San Francisco, California, United States
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
University of California, San Francisco
Investigators
Principal Investigator: Donald O'Rourke, MD Abramson Cancer Center of the University of Pennsylvania
Principal Investigator: Susan Chang, MD University of California, San Francisco
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02209376     History of Changes
Other Study ID Numbers: UPCC 35313
Study First Received: August 4, 2014
Last Updated: January 25, 2017

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on June 23, 2017