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

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Seattle Children's Healthcare System

Status and phase

Active, not recruiting
Phase 1

Conditions

Pineoblastoma
Choroid Plexus Carcinoma
Primitive Neuroectodermal Tumor
Germ Cell Tumor
Glioma
Central Nervous System Tumor, Pediatric
Medulloblastoma
Atypical Teratoid/Rhabdoid Tumor
Ependymoma

Treatments

Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell

Study type

Interventional

Funder types

Other

Identifiers

NCT03638167
BrainChild-02

Details and patient eligibility

About

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.

Enrollment

11 patients

Sex

All

Ages

1 to 26 years old

Volunteers

No Healthy Volunteers

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

  • 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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

11 participants in 2 patient groups

ARM A (Tumor Cavity Infusion)
Experimental group
Description:
Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
Treatment:
Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell
ARM B (Ventricular System Infusion)
Experimental group
Description:
Patients with either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the fourth ventricle or lateral ventricle, respectively
Treatment:
Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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