Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Description

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

Conditions

Central Nervous System Neoplasms, Atypical Teratoid/Rhabdoid Tumor, Diffuse Midline Glioma, H3 K27M-Mutant, Ependymoma, High Grade Glioma, Glioblastoma, Medulloblastoma

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Study Overview

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Study Details

Study overview

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Condition
Central Nervous System Neoplasms
Intervention / Treatment

-

Contacts and Locations

Memphis

St. Jude Children's Research Hospital, Memphis, Tennessee, United States, 38105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Age ≤ 21 years of age
  • 2. Primary CNS tumor
  • 3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor
  • 4. For Cohort B, must meet one of the following criteria:
  • * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \[IHC\] or H3K27M mutation if pontine lesion)
  • * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)
  • * Has presumptive/suspected brainstem high-grade neoplasm with available imaging for central imaging review
  • 5. Life expectancy of \> 12 weeks
  • 6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
  • 1. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.

Ages Eligible for Study

to 21 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

St. Jude Children's Research Hospital,

Christopher DeRenzo, MD, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

Kelsey Bertrand, MD, MSc, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

Giedre Krenciute, PhD, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

Study Record Dates

2028-03