Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors

Who is this study for? Patients with EGFR-positive recurrent or refractory pediatric central nervous system tumors
What treatments are being studied? EGFR806-specific chimeric antigen receptor T cell
Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 26
Healthy Volunteers: No
View:

• 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

Locations
United States
Washington
Seattle Children's Hospital
Recruiting
Seattle
Contact Information
Primary
Juliane Gust, MD, PhD
CBDCIntake@seattlechildrens.org
206-987-2106
Backup
Nicholas Vitanza, MD
CBDCIntake@seattlechildrens.org
206-987-2106
Time Frame
Start Date: March 19, 2019
Estimated Completion Date: March 2040
Participants
Target number of participants: 36
Treatments
Experimental: ARM A (Tumor Cavity Infusion)
Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
Experimental: ARM B (Ventricular System Infusion)
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
Sponsors
Leads: Seattle Children's Hospital

This content was sourced from clinicaltrials.gov

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