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| Name | Class |
|---|---|
| Kite Pharma (a Gilead Company) | UNKNOWN |
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This is an open-label phase 1 study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2 (referred to as "CART-EGFR-IL13Ra2 cells") in patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma, without evidence of disease recurrence/progression following completion of initial radiotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A (Single Fixed Dose) | Experimental | All subjects will receive a single fixed dose of CART-EGFR-IL13Ra2 cells on Day 0 via intracerebroventricular delivery. |
|
| Cohort B (Repeat Cycles Following Lymphodepletion) | Experimental | CART-EGFR-IL13Ra2 cells will be administered via intracerebroventricular delivery in q6 week cycles of treatment, following lymphodepletion with fludarabine, cyclophosphamide, and rituximab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CART-EGFR-IL13Ra2 cells | Drug | autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR epitope 806 and a humanized scFv targeting IL13Ra2; both scFvs are fused to the 4-1BB and CD3ζ signaling domains. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | Type, frequency, severity, and attribution of adverse events | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Occurrence of treatment-limiting toxicities (TLTs) | 28 days post-CAR T cell administration |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of enrolled subjects who receive study treatment as planned | Evaluated based on the proportion of subjects who screen fail and those who receive any dose of CART-EGFR-IL13Ra2 cells. | 28 days following initial treatment with CART-EGFR-IL13Ra2 cells |
| Proportion of eligible subjects who receive study treatment as planned |
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Step #1 Inclusion Criteria:
Step #1 Exclusion Criteria:
Step #2 Inclusion Criteria:
Patient completed full course of radiotherapy to 60 Gy.
No overt evidence of disease recurrence/progression post-radiotherapy confirmed by RANO 2.0 criteria.
Karnofsky Performance Status ≥ 60%
Adequate organ function defined as:
Step #2 Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials Service | Contact | 215-349-8245 | PMCancerResearch@pennmedicine.upenn.edu |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Bagley, MD, MSCE | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Rituximab or Rituximab biosimilar | Biological | 375 mg/m2/day x 1 day |
|
| Fludarabine + Cyclophosphamide combination | Drug | Fludarabine: 30mg/m2/day x 3 days; Cyclophosphamide: 300mg/m2/day x 3 days |
|
| 28 days following initial treatment with CART-EGFR-IL13Ra2 cells |
| Frequency of manufacturing failures | Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted. Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted. | 3 months |
| Progression-free Survival (PFS) | Per RANO 2.0 criteria | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Overall Survival (OS) | Time from initial study treatment to the date of death from any cause. | Up to 15 years following initial CART-EGFR-IL13Ra2 administration |
| Objective Response Rate (ORR) | Per RANO 2.0 criteria (in subjects with measurable disease at the time of study treatment); Proportion of subjects with confirmed CR and PR. | Up to 12 months following CART-EGFR-IL13Ra2 administration |
| Duration of response (DOR) | Per RANO 2.0 criteria (in subjects with measurable disease at the time of study treatment); Time from the date when a response of confirmed CR/PR is first met to the date of confirmed disease progression, death or receipt of alternative treatment other than CART-EGFR-IL13Ra2 retreatment. | Up to 15 years following initial CART-EGFR-IL13Ra2 administration |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |