IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Pediatric High-grade Glioma (HGG)

NCT06946680 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB202200057-POCR41673
• Study Type: interventional
• Target: 18
• 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 CD70+ pediatric high-grade glioma

Conditions

High-grade 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 (1)

8R-70CAR T cells

EXPERIMENTAL

Cohort 1 will receive 1 x 10\^6 cells/kg. Cohort 2 will receive 1 x 10\^7 cells/kg. Cohort 3 will receive 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

8R-70CAR T cells

Eligibility Criteria

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

You may qualify if:

• Newly-diagnosed pHGG based on the absence of a previous history of brain tumor (WHO Grade III-IV glioma) by histopathology.
• CD70 positive (≥5%, 1+) The tumors from the surgical resection or biopsy by immunohistochemistry will be confirmed by a validated assay performed at UF Health Pathology, a certified Lab.
• o 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: 0 = Negative
• = Low level
• = Moderate level
• Karnofsky Performance Status (KPS) or Lansky Performance Score (LPS) of \> 70% 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.
• CBC with differential with adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3.
• Platelet count ≥ 100,000 cells/mm3.
• Hemoglobin ≥ 10 g/dl. (The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
• Adequate renal function as defined below:
• o 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
• Adequate hepatic function as defined below:
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age
• ALT ≤ 3 times institutional upper limits of normal for age

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3years. (In situ cancer is permissible)
• Spinal metastasis and leptomeningeal involvement.
• Patients with Bulky Tumors:
• cm in a single dimension (post-surgery)
• Tumor causing uncal herniation or mass effect leading to midline shift with or without symptoms or signs of impending herniation or
• Obstruction to CSF flow
• Recurrent or multifocal malignant gliomas.
• The patient is not a candidate for cellular therapy as assessed by the study bone marrow transplant physician.
• Known immunosuppressive disease or human immunodeficiency virus (HIV) infection.
• HIV-positive patients are ineligible due to the unknown safety and efficacy of infusing these patients with CAR T cells genetically modified using retroviral vectors. Additionally, the immunosuppression used for treatment in this study will pose an unacceptable risk.
• Concurrent illness: Patients with active autoimmune disease, documented history of autoimmune disease/syndrome, or any other condition that requires ongoing systemic steroids or systemic immunosuppressive agents, except
• Patients with vitiligo or resolved asthma/atopy
• Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome
• Patients requiring physiologic doses of corticosteroids (up to 0.5 mg/m2/day dexamethasone equivalent)
• History of or ongoing pneumonitis or significant interstitial lung disease.

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; 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; 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

• Ashley Ghiaseddin, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 27, 2025
• Study Start: March 18, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2045
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)