Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors
2 other identifiers
interventional
48
1 country
1
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2023
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 23, 2023
CompletedStudy Start
First participant enrolled
April 27, 2023
CompletedFirst Posted
Study publicly available on registry
April 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2028
May 5, 2026
May 1, 2026
4.8 years
March 23, 2023
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD)
To determine the maximum tolerated dose for the locoregional delivery of autologous B7-H3-CAR T cells in patients with recurrent/refractory B7-H3- positive primary CNS tumors (Cohort A) or diffuse midline glioma (DMG) (Cohort B).
Four (4) weeks after the first B7-H3-CAR T-cell infusion or 7 days after the fourth B7-H3-CAR T cell infusion, whichever is longer
Secondary Outcomes (1)
Radiographic response
Four (4) weeks post B7-H3-CAR T-cell infusion
Study Arms (2)
Arm A (relapsed/refractory CNS tumors)
EXPERIMENTALPatients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.
Arm B (diffuse midline gliomas [DMG])
EXPERIMENTALPatients with DMG.
Interventions
Autologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells). Four (4) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.
Eligibility Criteria
You may qualify if:
- Age ≤ 21 years of age
- Primary CNS tumor
- For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor
- 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
- Life expectancy of \> 12 weeks
- Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
You may not qualify if:
- \. 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.
- Age ≤ 21 years of age
- Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:
- Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive
- Cohort B: Diffuse midline glioma AND tumor is:
- B7-H3 positive if non-pontine
- OR H3K27-altered diffuse midline pontine glioma
- OR radiographically-confirmed classic/typical DIPG
- Estimated life expectancy of \>12 weeks
- Karnofsky or Lansky performance score ≥50
- Participant of childbearing/child-fathering potential agrees to use contraception
- For females of childbearing age:
- Not pregnant with negative serum pregnancy test
- Not lactating with intent to breastfeed
- Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment
- +66 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher DeRenzo, MD
St. Jude Children's Research Hospital
- PRINCIPAL INVESTIGATOR
Kelsey Bertrand, MD, MSc
St. Jude Children's Research Hospital
- PRINCIPAL INVESTIGATOR
Giedre Krenciute, PhD
St. Jude Children's Research Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 23, 2023
First Posted
April 28, 2023
Study Start
April 27, 2023
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
March 1, 2028
Last Updated
May 5, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.