EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Brain Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 1 - 26 |
| Updated: | 4/6/2019 |
| Start Date: | March 19, 2019 |
| End Date: | January 2037 |
| Contact: | Juliane Gust, MD, PhD |
| Email: | CBDCIntake@seattlechildrens.org |
| Phone: | 206-987-2106 |
Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors
This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with
autologous CD4+ and CD8+ T cells that are lentivirally transduced to express an EGFR806
specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an
indwelling catheter into the tumor resection cavity or the ventricular system in children and
young adults with recurrent or refractory EGFR-positive CNS tumors. The primary objectives of
this protocol are to evaluate the feasibility, safety, and tolerability of CNS-delivered
fractionated CAR T cell infusions employing intra-patient dose escalation. Subjects with
supratentorial tumors will receive sequential EGFR806-specific CAR T cells delivered into the
tumor resection cavity, subjects with infratentorial tumors will receive sequential CAR T
cells delivered into the fourth ventricle, and subjects with leptomeningeal disease will
receive sequential CAR T cells delivered into the lateral ventricle. The secondary objectives
are to assess CAR T cell distribution within the cerebrospinal fluid (CSF), the extent to
which CAR T cells egress into the peripheral circulation, and EGFR expression at recurrence
of initially EGFR-positive tumors. Additionally, tumor response will be evaluated by magnetic
resonance imaging (MRI) and CSF cytology. The exploratory objectives are to analyze CSF
specimens for biomarkers of anti-tumor CAR T cell presence and functional activity.
autologous CD4+ and CD8+ T cells that are lentivirally transduced to express an EGFR806
specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an
indwelling catheter into the tumor resection cavity or the ventricular system in children and
young adults with recurrent or refractory EGFR-positive CNS tumors. The primary objectives of
this protocol are to evaluate the feasibility, safety, and tolerability of CNS-delivered
fractionated CAR T cell infusions employing intra-patient dose escalation. Subjects with
supratentorial tumors will receive sequential EGFR806-specific CAR T cells delivered into the
tumor resection cavity, subjects with infratentorial tumors will receive sequential CAR T
cells delivered into the fourth ventricle, and subjects with leptomeningeal disease will
receive sequential CAR T cells delivered into the lateral ventricle. The secondary objectives
are to assess CAR T cell distribution within the cerebrospinal fluid (CSF), the extent to
which CAR T cells egress into the peripheral circulation, and EGFR expression at recurrence
of initially EGFR-positive tumors. Additionally, tumor response will be evaluated by magnetic
resonance imaging (MRI) and CSF cytology. The exploratory objectives are to analyze CSF
specimens for biomarkers of anti-tumor CAR T cell presence and functional activity.
Inclusion Criteria:
- First 3 enrolled subjects: age ≥ 15 and ≤ 26 years Subsequent subjects: age ≥ 1 and ≤
26 years
- Histologically diagnosed EGFR positive Central Nervous System (CNS) tumor
- Evidence of refractory or recurrent CNS disease that has failed first-line therapy
- Tumor specimen available for evaluation of EGFR expression
- Able to tolerate apheresis
- CNS reservoir catheter, such as an Ommaya or Rickham catheter
- Life expectancy ≥ 8 weeks
- Lansky or Karnofsky score ≥ 60
- Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and
radiotherapy
- ≥ 7 days post last chemotherapy administration
- 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody
therapy
- No prior virotherapy. Prior genetically modified cell therapy is allowed if not
detectable at enrollment.
- Stable or decreasing dosing of steroid treatment for symptomatic relief from CNS
disease, with maximum dexamethasone dose of 2.5 mg/m2/day
- Adequate organ function
- Adequate laboratory values
- Subjects of childbearing/fathering potential must agree to use highly effective
contraception
- Subject and/or authorized legal representative signed a written consent
Exclusion Criteria:
- Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
- Presence of ≥ Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring
intervention
- Presence of primary immunodeficiency/bone marrow failure syndrome
- Presence of clinical and/or radiographic evidence of impending herniation
- Presence of active malignancy other than the primary CNS tumor under study
- Presence of active severe infection
- Receiving any anti-cancer agents or chemotherapy
- Pregnant or breastfeeding
- Subject and/or authorized legal representative unwilling to provide consent/assent for
participation in the 15 year follow up period
- Presence of any condition that, in the opinion of the investigator, would prohibit the
patient from undergoing treatment under this protocol
We found this trial at
1
site
4800 Sand Point Way NE
Seattle, Washington 98105
Seattle, Washington 98105
(206) 987-2000
Principal Investigator: Juliane Gust, MD, PhD
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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