IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Newly Diagnosed and Recurrent Pediatric High-grade Glioma (pHGG) and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (ndDIPG)

NCT06946680 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: IRB202600567OCR41673/IMPACT TrialIRB202200057-PPCR50548/Peds IMPACT
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in newly diagnosed and recurrent CD70+ Pediatric High-Grade Gliomas (pHGG) and Diffuse Intrinsic Pontine Glioma (ndDIPG)

Conditions

High-grade Glioma; Diffuse Intrinsic Pontine Glioma

Keywords

CAR T Cell; Brain Tumor; Brain Cancer; Immunotherapy; Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Incidence of investigational treatment related severe toxicity (Dose-limiting toxicity event)

  Safety is defined as the adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLT) observed throughout the trial.

  administration of 8R-70CAR T to 28 days post-infusion

• Prevalence of enrolled subjects who receive a qualified immunotherapy investigational product.

  Feasibility will be measured by the number of patients who receive 8R-70CAR T-cell that met the FDA IND defined quality assurance and quality control release criteria. A minimum of 66.7 % of enrolled subjects must achieve this criterion for the feasibility endpoint.

  Enrollment up to 18 weeks

• Maximum tolerated dose (MTD) dose-finding endpoint based on Dose-Limiting-Toxicity (DLT) incidence

  Determination of the maximum tolerated dose (MTD) of 8R-70CAR T cells based on the incidence of investigational treatment-related severe toxicity (dose-limiting toxicity events)

  administration of 8R-70CAR T to 28 days post-infusion

Study Arms (3)

Newly Diagnosed High Grade Glioma (ndHGG)

EXPERIMENTAL

Participants will receive either 8R-70CAR T 1 x 10\^7 cells/kg or 1 x 10\^8 cells/kg

Biological: Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells

Recurrent High Grade Glioma (rHGG)

EXPERIMENTAL

Participants will receive either 8R-70CAR T 1 x 10\^7 cells/kg or 1 x 10\^8 cells/kg

Biological: Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells

Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

EXPERIMENTAL

Participants will receive either 8R-70CAR T 1 x 10\^7 cells/kg or 1 x 10\^8 cells/kg

Biological: Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells

Interventions

Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells BIOLOGICAL

Single dose of 8R-70CAR T cells administered IV

Also known as: 8R-70CAR T cells

Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG); Newly Diagnosed High Grade Glioma (ndHGG); Recurrent High Grade Glioma (rHGG)

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• At enrollment:
• Patients with a histologically confirmed diagnosis of:
• Newly diagnosed high-grade glioma (WHO Grade III or IV)
• Newly diagnosed DIPG (after first 2 HGG patients are treated)
• Recurrent or progressive high-grade glioma
• Age 4-18 years old for ndHGG. Age 4-30 for rHGG. Age 4-30 for nd DIPG.

You may not qualify if:

• Patients with primary spinal cord tumors ARE eligible.
• CD70 positive (≥5%, 1+) The tumors from the surgical resection by immunohistochemistry will be confirmed by validated assay performed at UF Health Pathology, CLIA certified Lab.
• CD70 tumor expression performed on paraffin-embedded tumor specimens will be evaluated. Tumor expression will be scored on a scale of 0 to 3 staining intensity:
• = Negative
• = Low level
• = Moderate level
• Karnofsky Performance Status (KPS, for patients \>16yo) or Lansky Performance Score (LPS, for patients ≤16yo) of \> 60% (Appendix C)
• Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score provided the neurological deficit is stable.
• Organ Function:
• CBC with differential with adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3.
• Platelet count ≥ 75,000 cells/mm3. (Unsupported, no transfusion within 4 days.)
• Hemoglobin ≥ 8 g/dl. (May receive transfusions)
• Adequate renal function as defined below:
• Serum creatinine \< 1.5 x institutional upper limit of normal for age and gender. Patients who do not meet the criteria but have a 24-hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2 are eligible.

Sponsors & Collaborators

• University of Florida: lead
• Florida Department of Health, Live Like Bella: collaborator
• St. Baldrick's Foundation: collaborator
• American Brain Tumor Association: collaborator

Study Sites (1)

University of Florida Health Children's Hospital

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma; Brain Neoplasms; Glioblastoma

Interventions

Receptors, Interleukin-8B

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma

Intervention Hierarchy (Ancestors)

Receptors, Interleukin-8; Receptors, CXCR; Receptors, Chemokine; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Cytokine; Receptors, Immunologic; Receptors, Interleukin

Study Officials

• John Ligon, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer King, RN

CONTACT

352-273-9000; wells-BTC@ufl.edu

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: April 11, 2025
• First Posted: April 27, 2025
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2045
• Last Updated: July 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)