Seattle, Washington 98105


Purpose:

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.


Criteria:

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


NCT ID:

NCT03638167


Primary Contact:

Study Chair
Juliane Gust, MD, PhD
Seattle Children's Hospital

Juliane Gust, MD, PhD
Phone: 206-987-2106
Email: CBDCIntake@seattlechildrens.org


Backup Contact:

Email: CBDCIntake@seattlechildrens.org
Nicholas Vitanza, MD
Phone: 206-987-2106


Location Contact:

Seattle, Washington 98105
United States

Juliane Gust, MD, PhD

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: February 04, 2019

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