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Trial record 1 of 1 for:    NCT03638167
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EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors

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ClinicalTrials.gov Identifier: NCT03638167
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Julie Park, Seattle Children's Hospital

Tracking Information
First Submitted Date  ICMJE August 15, 2018
First Posted Date  ICMJE August 20, 2018
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE March 19, 2019
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • Safety: any adverse events associated with one or multiple EGFR806-specific CAR T cell product infusions will be assessed by CTCAE v5.0. [ Time Frame: up to 6 months ]
    The type, frequency, severity, and duration of adverse events as a result of EGFR806-specific CAR T cell infusion will be summarized
  • Feasibility: The number of successfully manufactured and infused EGFR806-specific CAR T cell product [ Time Frame: 28 days ]
    The proportion of products successfully manufactured and infused will be measured
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
  • Establish the safety, defined by the adverse events, of EGFR806-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system [ Time Frame: up to 6 months ]
    The type, frequency, severity, and duration of adverse events as a result of EGFR806-specific CAR T cell infusion will be summarized
  • Establish the feasibility, defined by the ability to produce and administer CAR T cell product, of EGFR806-specific CAR T cell product infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system [ Time Frame: 28 days ]
    The proportion of products successfully manufactured and infused will be measured
Change History Complete list of historical versions of study NCT03638167 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • 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 [ Time Frame: up to 6 months ]
    The trafficking of the EGFR806-specific CAR T cell product through the CSF by measuring remaining CAR T cells from a prior infusion at the time of each infusion and the trafficking of EGFR806-specific CAR T cells from the CSF into the peripheral blood will be evaluated.
  • Expression of target epitope: assessment of whether EGFR expression changes in relapsed CNS tumors that were EGFR positive prior to treatment with CAR T cells via immunohistochemistry on resected tissue samples. [ Time Frame: 28 days ]
    The changes in EGFR expression at diagnosis and recurrence of central nervous system (CNS) tumors, if samples from multiple time points is available, will be investigated by evaluating pathology specimens from previous surgeries
  • Disease response: Assessment of disease response of EGFR-expressing refractory or recurrent central nervous system (CNS) tumors to EGFR806 specific CAR T cell therapy delivered directly into the CNS by cytology and radiology criteria. [ Time Frame: up to 6 months ]
    The response of recurrent or refractory central EGFR-expressing CNS tumors to EGFR806-specific CAR T cell therapy delivered directly into the CNS will be determined by evaluating CSF for tumor cells and by CNS imaging with MRIs.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
  • Assess the distribution of CNS-delivered EGFR806-specific CAR T cells within the cerebrospinal fluid (CSF) and peripheral blood [ Time Frame: up to 6 months ]
    The trafficking of EGFR806-specific CAR T cell product through the CSF by measuring remaining CAR T cells from a prior infusion at the time of each infusion and the trafficking of EGFR806-specific CAR T cells from the CSF into the peripheral blood will be evaluated.
  • Assessment of whether EGFR expression changes in relapsed CNS tumors that were EGFR positive prior to treatment with CAR T cells [ Time Frame: 28 days ]
    The changes in EGFR expression at diagnosis and recurrence of central nervous system (CNS) tumors, if samples from multiple time points is available, will be investigated by evaluating pathology specimens from previous surgeries
  • Assessment of disease response of EGFR-expressing refractory or recurrent central nervous system (CNS) tumors to EGFR806 specific CAR T cell therapy delivered directly into the CNS [ Time Frame: up to 6 months ]
    The response of recurrent or refractory central EGFR-expressing CNS tumors to EGFR806-specific CAR T cell therapy delivered directly into the CNS will be determined by evaluating CSF for tumor cells and by CNS imaging with MRIs
Current Other Pre-specified Outcome Measures
 (submitted: August 30, 2018)
Quantitative biomarker assessment of anti tumor CAR T cell functional activity [ Time Frame: up to 6 months ]
The presence of biomarkers of anti-tumor CAR T cell functional activity, such as cytokines, will be quantified via protein expression analysis in CSF. These findings will be correlated with response by disease evaluations via CSF cytology and MRI imaging of the CNS.
Original Other Pre-specified Outcome Measures
 (submitted: August 15, 2018)
Analysis of CSF for biomarkers of anti tumor CAR T cell functional activity [ Time Frame: up to 6 months ]
The presence of biomarkers of anti-tumor CAR T cell functional activity in the CSF will be evaluated and correlated with response by disease evaluations of the CSF and by CNS imaging with MRIs
 
Descriptive Information
Brief Title  ICMJE EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
Official Title  ICMJE 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Central Nervous System Tumor, Pediatric
  • Glioma
  • Ependymoma
  • Medulloblastoma
  • Germ Cell Tumor
  • Atypical Teratoid/Rhabdoid Tumor
  • Primitive Neuroectodermal Tumor
  • Choroid Plexus Carcinoma
  • Pineoblastoma
Intervention  ICMJE Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell
Autologous CD4+ and CD8+ T cells lentivirally transduced to express an EGFR806 specific chimeric antigen receptor (CAR) and EGFRt given via indwelling central nervous system (CNS) catheter
Study Arms  ICMJE
  • Experimental: ARM A (Tumor Cavity Infusion)
    Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
    Intervention: Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell
  • 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
    Intervention: Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 15, 2018)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2037
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 26 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Juliane Gust, MD, PhD 206-987-2106 CBDCIntake@seattlechildrens.org
Contact: Nicholas Vitanza, MD 206-987-2106 CBDCIntake@seattlechildrens.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03638167
Other Study ID Numbers  ICMJE BrainChild-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Julie Park, Seattle Children's Hospital
Study Sponsor  ICMJE Seattle Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Juliane Gust, MD, PhD Seattle Children's Hospital
PRS Account Seattle Children's Hospital
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP