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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

Tracking Information
First Submitted Date  ICMJE August 4, 2014
First Posted Date  ICMJE August 5, 2014
Last Update Posted Date March 5, 2019
Actual Study Start Date  ICMJE November 18, 2014
Actual Primary Completion Date April 4, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2014)
Number of adverse events [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
Official Title  ICMJE Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Patients With Residual or Reccurent EGFRvIII+ Glioma
Intervention  ICMJE Biological: CART-EGFRvIII T cells
Study Arms  ICMJE Experimental: Arm 1
Intervention: Biological: CART-EGFRvIII T cells
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 4, 2019)
11
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2014)
12
Actual Study Completion Date  ICMJE April 4, 2018
Actual Primary Completion Date April 4, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02209376
Other Study ID Numbers  ICMJE UPCC 35313, 820381
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE University of California, San Francisco
Investigators  ICMJE
Principal Investigator: Donald O'Rourke, MD Abramson Cancer Center of the University of Pennsylvania
Principal Investigator: Susan Chang, MD University of California, San Francisco
PRS Account University of Pennsylvania
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP