Status:
RECRUITING
IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Pediatric High-grade Glioma (HGG)
Lead Sponsor:
University of Florida
Collaborating Sponsors:
Florida Department of Health, Live Like Bella
St. Baldrick's Foundation
Conditions:
High-grade Glioma
Eligibility:
All Genders
4-18 years
Phase:
PHASE1
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
Detailed Description
Identified newly-diagnosed pediatric CD70+ HGG patients will be enrolled in this clinical trial study prior to initiation of standard-of-care chemo-radiation. Prior to initiation of chemoradiation, PB...
Eligibility Criteria
Inclusion
- 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
- = High level The criteria for inclusion will be at least 5% of the cells scoring 1+ staining intensity (\> 5%, 1+).
- 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
- AST ≤ 3 times institutional upper limits of normal for age
- Signed informed consent, or for patients age \<18, parental permission, and, as appropriate, assent from pediatric patients age ≥12. If the patient's mental status precludes their informed consent, the legally authorized representative may give informed consent. Consent or permission/assent will be obtained at screening (before PBMC collection) and before treatment with CAR T-cells.
- 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
- 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:
- 3 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.
- Ongoing or active uncontrolled infection.
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator, would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.
- Patients with any of the following cardiac diseases:
- New York Heart Association (NYHA) functional class III or IV
- Clinically significant cardiac arrhythmia including, but not limited to, Torsade de pointes or requiring a pacemaker
- Left ventricular ejection fraction below 50% as determined by echocardiography (ECHO)
- 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.
- For females of childbearing potential, a negative serum pregnancy test at enrollment.
Key Trial Info
Start Date :
March 18 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2045
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT06946680
Start Date
March 18 2025
End Date
December 1 2045
Last Update
January 8 2026
Active Locations (1)
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1
University of Florida Health Children's Hospital
Gainesville, Florida, United States, 32608