search
Back to results

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors

Primary Purpose

Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, Recurrent CNS Tumor, Adult

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SC-CAR4BRAIN
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma focused on measuring CNS Tumor, DIPG, DMG, B7-H3, HER2, IL13-zetakine, EGFR806, CAR T cell, pediatric, brain tumor

Eligibility Criteria

1 Year - 26 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects must be age ≥ 1 and ≤ 26 years (except for the first 3 subjects, who must be age ≥ 12 and ≤ 26 years). Subject disease classified as one of the following: DIPG at any timepoint following completion of standard radiotherapy DMG at any timepoint following completion of standard radiotherapy Evidence of refractory or recurrent CNS disease for which there is no routine therapy, defined by either of the following: i. New site or sites of measurable or evaluable disease by radiographic imaging or histologic confirmation following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable, OR ii. Measurable or evaluable disease that persists following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable Able to tolerate apheresis or already has an apheresis product available for use in manufacturing CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy delivered as specified for BrainChild-04 Life expectancy ≥ 8 weeks Lansky or Karnofsky score ≥ 60. If patient does not have previously obtained apheresis product, patient must have discontinued, and 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 from the time of enrollment through 12 months following the last T cell infusion Exclusion Criteria: 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 in the CNS For Arm A subjects only: Presence of > Grade 3 dysphagia Presence of active malignancy other than the CNS tumor under study Presence of active severe infection, defined as either of the following: Positive blood culture within 48 hours of enrollment, OR Fever > 38.2ºC AND clinical signs of infection within 48 hours of enrollment Pregnant or breastfeeding Subject and/or authorized legal representative unwilling to provide consent/assent for study participation, including participation in the 15-year follow-up period, which is required if CAR T cell therapy is administered Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

Sites / Locations

  • Seattle Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A - DIPG

Arm B - DMG & recurrent/refractory tumors

Arm Description

Outcomes

Primary Outcome Measures

Manufacturing Feasibility
Number and percent of subjects with sufficient therapeutic product generated to receive two courses on the intended dose regimen
Safety of SC-CAR4BRAIN
Establish the safety, defined by the adverse events of fractionated intraventricular CNS administration of adoptive therapy with SC-CAR4BRAIN in children and young adults with DIPG, DMG, or recurrent/refractory CNS tumors
Dose level
Establish the maximally tolerated dose regimen (MTDR) and recommended Phase 2 dose regimen (RP2DR) of fractionated intraventricular CNS administered SC CAR4BRAIN infusions.
Administration feasibility
Number of subjects meeting criteria for their initial CAR T infusion and number of subjects meeting criteria for at least 2 courses of CAR T infusions

Secondary Outcome Measures

Full Information

First Posted
February 17, 2023
Last Updated
June 27, 2023
Sponsor
Seattle Children's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05768880
Brief Title
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
Official Title
Phase 1 Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 5, 2023 (Actual)
Primary Completion Date
January 15, 2028 (Anticipated)
Study Completion Date
December 31, 2043 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with SC-CAR4BRAIN, an autologous CD4+ and CD8+ T cells lentivirally transduced to express to express combinations of B7-H3, EGFR806, HER2, and IL13-zetakine chimeric antigen receptors (CAR). CAR T cells are delivered via an indwelling catheter into the ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors. A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into their ventricular system, and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that target B7H3, EGFR806, HER2, and IL13-zetakine on tumor cells. Patients will be assigned to 1 of 2 treatment Arms based on the type of their tumor: Arm A is for patients with DIPG (meaning primary disease localized to the pons, metastatic disease is allowed) anytime after standard radiation OR after progression. Arm B is for patients with non-pontine DMG (meaning DMG in other parts of the brain such as the thalamus or spine) anytime after standard radiation OR after progression. This Arm also includes other recurrent/refractory CNS tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, Recurrent CNS Tumor, Adult, Recurrent, CNS Tumor, Childhood, Refractory Primary Malignant Central Nervous System Neoplasm
Keywords
CNS Tumor, DIPG, DMG, B7-H3, HER2, IL13-zetakine, EGFR806, CAR T cell, pediatric, brain tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A - DIPG
Arm Type
Experimental
Arm Title
Arm B - DMG & recurrent/refractory tumors
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
SC-CAR4BRAIN
Intervention Description
Courses of weekly intravenous SC-CAR4BRAIN infusions for 3 weeks, then 1 week off
Primary Outcome Measure Information:
Title
Manufacturing Feasibility
Description
Number and percent of subjects with sufficient therapeutic product generated to receive two courses on the intended dose regimen
Time Frame
42 days
Title
Safety of SC-CAR4BRAIN
Description
Establish the safety, defined by the adverse events of fractionated intraventricular CNS administration of adoptive therapy with SC-CAR4BRAIN in children and young adults with DIPG, DMG, or recurrent/refractory CNS tumors
Time Frame
28 days post-final SC-CAR4BRAIN infusion
Title
Dose level
Description
Establish the maximally tolerated dose regimen (MTDR) and recommended Phase 2 dose regimen (RP2DR) of fractionated intraventricular CNS administered SC CAR4BRAIN infusions.
Time Frame
28 days
Title
Administration feasibility
Description
Number of subjects meeting criteria for their initial CAR T infusion and number of subjects meeting criteria for at least 2 courses of CAR T infusions
Time Frame
98 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must be age ≥ 1 and ≤ 26 years (except for the first 3 subjects, who must be age ≥ 12 and ≤ 26 years). Subject disease classified as one of the following: DIPG at any timepoint following completion of standard radiotherapy DMG at any timepoint following completion of standard radiotherapy Evidence of refractory or recurrent CNS disease for which there is no routine therapy, defined by either of the following: i. New site or sites of measurable or evaluable disease by radiographic imaging or histologic confirmation following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable, OR ii. Measurable or evaluable disease that persists following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable Able to tolerate apheresis or already has an apheresis product available for use in manufacturing CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy delivered as specified for BrainChild-04 Life expectancy ≥ 8 weeks Lansky or Karnofsky score ≥ 60. If patient does not have previously obtained apheresis product, patient must have discontinued, and 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 from the time of enrollment through 12 months following the last T cell infusion Exclusion Criteria: 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 in the CNS For Arm A subjects only: Presence of > Grade 3 dysphagia Presence of active malignancy other than the CNS tumor under study Presence of active severe infection, defined as either of the following: Positive blood culture within 48 hours of enrollment, OR Fever > 38.2ºC AND clinical signs of infection within 48 hours of enrollment Pregnant or breastfeeding Subject and/or authorized legal representative unwilling to provide consent/assent for study participation, including participation in the 15-year follow-up period, which is required if CAR T cell therapy is administered Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nick Vitanza, MD
Phone
206-987-2106
Email
CBDCIntake@seattlechildrens.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nick Vitanza, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Rebecca Ronsley, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Ronsley, MD
Phone
206-987-2106
Email
CBDCIntake@seattlechildrens.org
First Name & Middle Initial & Last Name & Degree
Rebecca Ronsley, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors

We'll reach out to this number within 24 hrs