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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02209376
Recruitment Status : Terminated (Sponsor decision to terminate prior to completion to pursue combination therapies.)
First Posted : August 5, 2014
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
University of Pennsylvania

Study Description
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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 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 or disease Intervention/treatment Phase
Patients With Residual or Reccurent EGFRvIII+ Glioma Biological: CART-EGFRvIII T cells Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
Actual Study Start Date : November 18, 2014
Actual Primary Completion Date : April 4, 2018
Actual Study Completion Date : April 4, 2018

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1 Biological: CART-EGFRvIII T cells


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

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02209376


Locations
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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
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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
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02209376    
Other Study ID Numbers: UPCC 35313, 820381
First Posted: August 5, 2014    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue