EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma (ExCeL)
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|ClinicalTrials.gov Identifier: NCT02664363|
Recruitment Status : Terminated (Study funding ended)
First Posted : January 27, 2016
Results First Posted : July 24, 2020
Last Update Posted : July 24, 2020
Please note that enrollment on this study terminated early due to the end of grant funding.
Newly diagnosed WHO grade IV malignant glioma subjects who are eligible were enrolled following surgery to remove their brain tumor. They then underwent 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 was completed, subjects returned for the post-RT brain imaging assessment, and, if stable, started post-RT TMZ cycles. Patients received up to 3 cycles of dose-intensified TMZ prior to receiving the EGFRvIII CAR T cells, which was infused in dose escalation cohorts. Following a one-month delay between cycles, the subject resumed post-RT cycles of TMZ and were monitored with blood work and brain imaging as per SOC.
An expanded cohort of 12 subjects was originally planned for once the maximally tolerated dose (MTD) was reached in the dose escalation cohorts, in order 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) was planned 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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Completion Date :||September 12, 2019|
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.
- Maximally Tolerated Dose [ Time Frame: 12-18 months ]Within this "3+3" phase I study, the primary objective is to determine the MTD of a single IV infusion of EGFRvIII CAR T cells in patients with newly-diagnosed WHO grade IV malignant glioma. Four dose levels were to be considered based on transduced cells/kg: #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. The MTD is the highest dose level at which ≤1 of 3-6 patients experience dose-limiting toxicity during the 4 weeks after CAR infusion.
- Number of Patients Who Experienced a Dose-limiting Toxicity (DLT) [ Time Frame: 12-18 months ]DLT is defined as any Grade IV event of any duration that is at least (possibly, probably, or definitely) attributable to EGFRvIII CARs, or any Grade III toxicity that is at least (possibly, probably, or definitely) attributable to EGFRvIII CARs that is not reversible within 4 weeks.
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
|United States, North Carolina|
|The Preston Robert Tisch Brain Tumor Center at Duke|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David Ashley, MBBS, FRACP, PhD||Duke University Hospital|
|Principal Investigator:||Daniel Landi, MD||Duke University|