EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors

  • STATUS
    Recruiting
  • End date
    Mar 25, 2040
  • participants needed
    36
  • sponsor
    Seattle Children's Hospital
Updated on 25 March 2022
tumor resection
MRI
dexamethasone
EGFR
apheresis
cns disease
cancer chemotherapy
supratentorial tumors
cns tumor
tumour resection
cns neoplasm
viral therapy
posterior fossa tumors
central nervous system tumor
mg++

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.

Details
Condition Central Nervous System Tumor, Pediatric, Glioma, Ependymoma, Medulloblastoma, Germ Cell Tumor, Atypical Teratoid/Rhabdoid Tumor, Primitive Neuroectodermal Tumor, Choroid Plexus Carcinoma, Pineoblastoma
Treatment EGFR806-specific chimeric antigen receptor (CAR) T cell
Clinical Study IdentifierNCT03638167
SponsorSeattle Children's Hospital
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age ≥ 15 and ≤ 26 years
Histologically diagnosed EGFR positive Central Nervous System (CNS) tumor
Evidence of refractory or recurrent CNS disease for which there is no standard therapy
Able to tolerate apheresis or apheresis product available for use in manufacturing
CNS reservoir catheter, such as an Ommaya or Rickham catheter
Life expectancy ≥ 8 weeks
Lansky or Karnofsky score ≥ 60
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
≥ 7 days post last chemotherapy/biologic therapy administration
3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy
Must be at least 30 days from most recent cellular infusion
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
Adequate organ function
Adequate laboratory values
Subjects of childbearing/fathering potential must agree to use highly effective contraception

Exclusion Criteria

Presence of ≥ Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention
Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
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
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