Brief Title
EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
Official Title
Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors
Brief Summary
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 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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Safety: any adverse events associated with one or multiple EGFR806-specific CAR T cell product infusions will be assessed by CTCAE v5.0.
Secondary Outcome
CAR T cell distribution: The number of subjects with CAR T cell persistence in the cerebrospinal fluid (CSF) and peripheral blood as measured by flow cytometry
Condition
Central Nervous System Tumor, Pediatric
Intervention
EGFR806-specific chimeric antigen receptor (CAR) T cell
Study Arms / Comparison Groups
ARM A (Tumor Cavity Infusion)
Description: Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
36
Start Date
March 19, 2019
Completion Date
March 2040
Primary Completion Date
March 2025
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 15 and ≤ 26 years
2. Histologically diagnosed EGFR positive Central Nervous System (CNS) tumor
3. Evidence of refractory or recurrent CNS disease for which there is no standard therapy
4. Able to tolerate apheresis or apheresis product available for use in manufacturing
5. CNS reservoir catheter, such as an Ommaya or Rickham catheter
6. Life expectancy ≥ 8 weeks
7. Lansky or Karnofsky score ≥ 60
8. If patient does not have previously obtained apheresis product, patient must have
recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and
radiotherapy and discontinue the following prior to enrollment:
1. ≥ 7 days post last chemotherapy/biologic therapy administration
2. 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor
antibody therapy
3. Must be at least 30 days from most recent cellular infusion
4. All systemically administered corticosteroid treatment therapy must be stable or
decreasing within 1 week prior to enrollment with maximum dexamethasone dose of
2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed.
9. Adequate organ function
10. Adequate laboratory values
11. Subjects of childbearing/fathering potential must agree to use highly effective
contraception
Exclusion Criteria:
1. Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
2. Presence of ≥ Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring
intervention
3. Presence of primary immunodeficiency/bone marrow failure syndrome
4. Presence of clinical and/or radiographic evidence of impending herniation
5. Presence of active malignancy other than the primary CNS tumor under study
6. Presence of active severe infection
7. Receiving any anti-cancer agents or chemotherapy
8. Pregnant or breastfeeding
9. Subject and/or authorized legal representative unwilling to provide consent/assent for
participation in the 15 year follow up period
10. Presence of any condition that, in the opinion of the investigator, would prohibit the
patient from undergoing treatment under this protocol
Gender
All
Ages
1 Year - 26 Years
Accepts Healthy Volunteers
No
Contacts
Juliane Gust, MD, PhD, 206-987-2106, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03638167
Organization ID
BrainChild-02
Responsible Party
Principal Investigator
Study Sponsor
Seattle Children's Hospital
Study Sponsor
Juliane Gust, MD, PhD, Study Chair, Seattle Children's Hospital
Verification Date
March 2021