IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma

NCT05353530 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB202200057-AOCR41673
• Study Type: interventional
• Target: 39
• 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+ adult glioblastoma

Conditions

Glioblastoma Multiforme; Glioblastoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Safety of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM

  Defined as ≤ 1 DLT out of 6 patients is observed at the 1x10\^8 cells/Kg dose. Dose-Limiting toxicity (DLT) will be defined as any adverse event attributable (possible, probable, or definite) to the administration of 8R-70CAR T cells and occurring from the time of infusion through 28 days post-infusion.

  28 days post-infusion

• Feasibility of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM

  Feasibility will be defined as the ability to infuse 8R-70CAR T-cell safely in 66.7 % of enrolled patients (patients who signed consent and were deemed eligible for the study).

  10 weeks

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. Cohort 4 will receive Cy/Flu + CAR T cells at established maximum tolerated dose.

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: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Newly-diagnosed de novo GBM based on the absence of previous history of brain tumor (WHO Grade IV glioma) by histopathology or molecular studies. (secondary GBM not eligible)
• The tumor must have a supratentorial component
• CD70 positive (≥5%, 1+)
• Tumor expression will be scored on a scale of 0 to 3 staining intensity:
• = Negative
• = Low level
• = Moderate level
• = High level
• Surgical resection of tumors with less than 3cm x 3cm (9 cm2) residual enhancing tumor as a product of longest perpendicular planes by MRI or biopsy only for tumor measuring less than 3cm x 3cm
• Karnofsky Performance Status (KPS) of \> 70%
• CBC with differential with adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1500 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.)

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3years. (In situ cancer are permissible)
• Metastases detected below the tentorium or beyond the cranial vault
• Leptomeningeal disease beyond the cranial vault. (Focal, adjacent and leptomeningeal involvement is allowable at the discretion of the PI).
• 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.
• Rationale: The need to exclude patients with the immunosuppressive disease or human
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization.
• Transmural myocardial infarction within the last 6 months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the initiation of XRT/TMZ.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the initiation of XRT/TMZ.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
• Patients with an autoimmune disease requiring medical management with immunosuppressants.
• Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.

Sponsors & Collaborators

• University of Florida: lead
• AM Rosen Foundation: collaborator

Study Sites (1)

University of Florida Health

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Receptors, Interleukin-8B

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; 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

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 25, 2022
• First Posted: April 29, 2022
• Study Start: July 25, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2042
• Last Updated: March 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)