Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

Part of paid clinical trials in Seattle, Washington.

Sponsor
Seattle Children's Hospital
Study ID
NCT04185038
Phase
PHASE1
Status
Recruiting
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Conditions

  • Atypical Teratoid/Rhabdoid Tumor
  • Central Nervous System Tumor
  • Choroid Plexus Carcinoma
  • Diffuse Intrinsic Pontine Glioma
  • Diffuse Midline Glioma
  • Ependymoma
  • Germ Cell Tumor
  • Glioma
  • Medulloblastoma, Childhood
  • Pineoblastoma, Childhood
  • Primitive Neuroectodermal Tumor

Eligibility Criteria

Sex
ALL
Age
1 Year - 26 Years
Healthy Volunteers
Not accepted

Interventions

  • SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel — BIOLOGICAL
    Autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) and EGFRt given via indwelling central nervous system (CNS) catheter

Study Details

This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or 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 the tumor resection cavity or 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 targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available. The hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.

Key Dates

Start date
Dec 11, 2019
Status verified
Apr 2026
Primary completion
May 31, 2027
Completion
May 31, 2042

Study Design

Enrollment
90 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: ARM A (Tumor Cavity Infusion) - [CLOSED TO ENROLLMENT]
    Patients with non-DIPG supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
  • Experimental: ARM B (Ventricular System Infusion) - [CLOSED TO ENROLLMENT]
    Patients with non-DIPG either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the ventricular system
  • Experimental: ARM C (DIPG) - [CLOSED TO ENROLLMENT]
    Patients with DIPG for whom CAR T cells will be delivered into the ventricular system
  • Experimental: Arm D (Non-pontine DMG)
    Patients with non-pontine DMG for whom CAR T cells will be delivered into the ventricular system
  • Experimental: Arm E
    Patients with DIPG who will receive up to 15 doses of CAR T cells delivered into the ventricular system

Primary Outcome Measure

Establish the safety, defined by the adverse events, of B7H3-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 7 months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Seattle Children's HospitalSeattleWashington98105
Nick Vitanza, MD
[email protected]
206-987-2106
Rebecca Ronsley, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in Seattle, WA

By condition
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By specialty
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By research site
Seattle Children's Hospital· Seattle, WA

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