IL-8 receptor modified CAR T cell therapy for adult glioblastoma

Phase I Study -To Assess Safety and Feasibility of IL-8 Receptor Modified Patient-derived Activated CD70 CAR T Cell Therapy in CD70+ Adult GBM and Pediatric High-Grade Gliomas (pHGG)

This study is testing a new type of CAR T cell therapy to see if it can safely help adults with a specific type of brain cancer called glioblastoma after they have had surgery and standard treatment.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: University of Florida (other)
• Drugs / interventions: radiation, CAR T, Immunotherapy
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT05353530 on ClinicalTrials.gov

What this trial studies

This phase I clinical trial evaluates the safety and feasibility of using IL-8 receptor modified CD70 CAR T cell therapy in patients with CD70 positive adult glioblastoma. Participants will have undergone surgery for tumor removal and will receive standard chemoradiation before being administered a single dose of the modified CAR T cells. The study follows a dose-escalation design to determine the optimal dose of the therapy. The trial aims to assess the immune response and potential therapeutic benefits of this innovative approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed CD70 positive glioblastoma who have undergone surgical resection.

Not a fit: Patients with secondary glioblastoma or those who have not undergone surgical resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option for patients with CD70 positive glioblastoma, potentially improving survival rates.

How similar studies have performed: While CAR T cell therapies have shown promise in other cancers, this specific approach targeting CD70 in glioblastoma is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria (Adult GBM):

* 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 (≥20%, 1+)

Tumor expression will be scored on a scale of 0 to 3 staining intensity:

0 = Negative

1. = Low level
2. = Moderate level
3. = High level

   * The criteria for inclusion will be at least 20% of the cells scoring 1+ staining intensity (\> 20%, 1+).

     * Surgical resection of tumors with less than 3cm x 3cm (9 cm2) residual enhancing tumor as a product of longest perpendicular planes by MRI. (biopsy only subjects are not eligible for this study)
     * 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.)

     • Adequate renal function as defined below:
   * BUN ≤ 25 mg/dl
   * Creatinine ≤ 1.7 mg/dl

     • Adequate hepatic function as defined below:
   * Bilirubin ≤ 2.0 mg/dl
   * ALT ≤ 5 times institutional upper limits of normal for age
   * AST ≤ 5 times institutional upper limits of normal for age

     * Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative.
     * For females of childbearing potential, a negative serum pregnancy test at enrollment.
     * Women of childbearing potential (WOCBP) must be willing to use an acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
     * Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

Exclusion Criteria (Adult GBM):

* 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.
  * Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity.
* Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant.
* Patients treated on any other therapeutic clinical protocols within 30 days prior to enrollment.

Where this trial is running

Gainesville, Florida

• University of Florida Health — Gainesville, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Ashley Ghiaseddin, MD — University of Florida
• Study coordinator: Phuong Deleyrolle, RN

Conditions: Glioblastoma Multiforme, Glioblastoma, CAR T Cell, Brain Tumor, Brain Cancer, Immunotherapy