Clinical trial · Interventional
EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma
EGFRvIII Chimeric Antigen Receptor (CAR) Gene-modified T Cells for Patients With Newly-Diagnosed GBM During Lymphopenia
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Study funding ended
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
| Gliosarcoma | Gliosarcoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| EGFRvIII CAR T cells | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- EGFRvIII CAR T cells
- description
- 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.
- interventionNames
- Biological: EGFRvIII CAR T cells
Primary outcomes (1)
- measure
- Maximally Tolerated Dose
- timeFrame
- 12-18 months
- description
- 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.
Secondary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria: 1. Age 18-80 years of age 2. Histopathologically proven newly-diagnosed, supratentorial glioblastoma or gliosarcoma (World Health Organization \[WHO\] Grade IV) 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
References
Publications (1)
- DERIVEDSuryadevara CM, Desai R, Abel ML, Riccione KA, Batich KA, Shen SH, Chongsathidkiet P, Gedeon PC, Elsamadicy AA, Snyder DJ, Herndon JE 2nd, Healy P, Archer GE, Choi BD, Fecci PE, Sampson JH, Sanchez-Perez L. Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma. Oncoimmunology. 2018 Feb 21;7(6):e1434464. doi: 10.1080/2162402X.2018.1434464. eCollection 2018. PMID 29872570