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EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma (ExCeL)

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: NCT02664363
Recruitment Status : Active, not recruiting
First Posted : January 27, 2016
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief Summary:
Newly diagnosed WHO grade IV malignant glioma subjects who are eligible will be enrolled following surgery to remove the brain tumor. They will then undergo a leukapheresis to harvest cells for the generation of the study drug, Epidermal Growth Factor variant III Chimeric Antigen Receptor (EGFRvIII CAR) T cells prior to beginning standard of care (SOC) radiation therapy (RT) with temozolomide (TMZ). Once SOC RT with TMZ is completed, subjects will return for the post-RT brain imaging assessment, and if stable will start post-RT TMZ cycles. Patients will receive up to 3 cycles of dose intensified TMZ prior to receiving the EGFRvIII CAR T cells, which will be infused in dose escalation cohorts. Following a one month delay between cycles, the subject will resume post-RT cycles of TMZ and be monitored with blood work and brain imaging as per SOC. Once the maximally tolerated dose (MTD) is reached in the dose escalation cohorts, an expanded cohort of 12 subjects will be enrolled to obtain a more precise estimate of the probability of unacceptable toxicity and to track the EGFRvIII CAR T cells using 111 Indium (111In) labeling. Computed Tomography (CT) will be done on days 1, 2, and 3 post-infusion to determine intracerebral (IC) localization.

Condition or disease Intervention/treatment Phase
Glioblastoma Gliosarcoma Biological: EGFRvIII CAR T cells Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: EGFRvIII Chimeric Antigen Receptor (CAR) Gene-modified T Cells for Patients With Newly-Diagnosed GBM During Lymphopenia
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : September 25, 2018
Estimated Study Completion Date : September 25, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: EGFRvIII CAR T cells
Dose escalation cohorts for 4 dose levels will be considered: #1: 4.5 x 10^6/kg, #2: 1.5 x 10^7/kg, #3: 4.5 x 10^7/kg, and #4: 1.5 x 10^8/kg. Starting at dose level 1, cohorts of 3-6 subjects will be accrued at each dose level.
Biological: EGFRvIII CAR T cells
The name of the drug is CAR gene-modified T cells or abbreviated as EGFRvIII CARs. The class of action is a biological and the mechanism of action is cytotoxicity. The drug substance is autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII. EGFRvIII CARs are genetically engineered T cells that have been taken from patients with GBM ex vivo to express a CAR recognizing the GBM tumor-specific antigen EGFRvIII, which is expressed on a subset of GBMs but not in normal human tissues with the aim of mediating regression of their tumors. Patients' CARs will be radiolabeled with 111In for correlative studies in the expanded cohort.
Other Names:
  • EGFRvIII CARs
  • CAR-specific T cells
  • CAR T cells
  • CARs
  • 111Indium Labeled EGFRvIII CARs
  • 111In-Labeled EGFRvIII CARs
  • CAR gene-modified T cells
  • 111In-labeled CARs




Primary Outcome Measures :
  1. MTD [ Time Frame: 12-18 months ]
    The primary objective is to determine the MTD of a single IV infusion of EGFRvIII CAR T cells in patients with newly-diagnosed GBM.


Secondary Outcome Measures :
  1. DLT [ Time Frame: 12-18 months ]
    To determine the DLT of a single IV infusion EGFRvIII CAR T cells in patients with newly-diagnosed GBM.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-80 years of age
  2. Histopathologically proven newly-diagnosed, supratentorial malignant primary brain tumor (World Health Organization (WHO) Grade IV GBM).
  3. Karnofsky Performance Status (KPS) score ≥ 70.
  4. The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry (IHC) or Polymerase Chain Reaction (PCR).
  5. Hematology:

    • Absolute Neutrophil Count (ANC) ≥ 1000/mm^3 without the support of filgrastim
    • Platelet count ≥ 100,000/mm^3
    • Hemoglobin ≥ 8.0 g/dl (eligibility level for hemoglobin may be reached with transfusion).
  6. Chemistry:

    • Alanine Amino Transferase (ALT)/Aspartate Amino Transferase (AST) ≤ 2.5 times the upper limit of normal
    • Creatinine ≤ 1.6 mg/dl
    • Total bilirubin ≤ 1.5 mg/dl.

Exclusion Criteria:

  1. Patients who are pregnant, breast-feeding, or unwilling to practice an effective method of birth control.
  2. Patients with known potentially anaphylactic allergic reactions to Gadolinium-Diethylene Triamine Pentaacetic Acid (gd-DTPA).
  3. Patients who cannot undergo Magnetic Resonance Imaging (MRI) or Single Photon Emission-Computed Tomography (SPECT) due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates).
  4. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, or with evidence of leptomeningeal disease.
  5. Active infection requiring treatment or an unexplained febrile (> 101.5 F) illness.
  6. Known autoimmune disease, immunosuppressive disease or human immunodeficiency virus (HIV) infection (i.e., known HIV or Hepatitis C).
  7. Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease.
  8. Patients with previous history of radiosurgery, brachytherapy, gliadel implantation, or radiolabeled monoclonal antibodies.
  9. Prior antitumor therapy for glioma (other than steroids).
  10. Allergic to TMZ.

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): NCT02664363


Locations
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United States, North Carolina
The Preston Robert Tisch Brain Tumor Center at Duke
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Gary Archer Ph.D.
Investigators
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Principal Investigator: David Ashley, MBBS, FRACP, PhD Duke University Hospital
Principal Investigator: Daniel Landi, MD Duke University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gary Archer Ph.D., Assistant Professor, Duke University
ClinicalTrials.gov Identifier: NCT02664363     History of Changes
Other Study ID Numbers: Pro00069444
First Posted: January 27, 2016    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue