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

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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