RECRUITING

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

Conditions

High-grade Glioma CAR T Cell Brain Tumor Brain Cancer Immunotherapy Glioblastoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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)

Quick Facts

Study Start:2025-05

Study Completion:2045-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06946680

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Years to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Newly-diagnosed pHGG based on the absence of a previous history of brain tumor (WHO Grade III-IV glioma) by histopathology. * CD70 positive (≥20%, 1+) The tumors from the surgical resection by immunohistochemistry will be confirmed by a validated assay performed at UF Health Pathology, a certified Lab. 1. = Low level 2. = Moderate level 3. = High level * Karnofsky Performance Status (KPS) or Lansky Performance Score (LPS) of \> 70% (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. * 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: * 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.	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* Newly-diagnosed pHGG based on the absence of a previous history of brain tumor (WHO Grade III-IV glioma) by histopathology.
* CD70 positive (≥20%, 1+) The tumors from the surgical resection by immunohistochemistry will be confirmed by a validated assay performed at UF Health Pathology, a certified Lab.
1. = Low level
2. = Moderate level
3. = High level
* Karnofsky Performance Status (KPS) or Lansky Performance Score (LPS) of \> 70% (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.
* 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:
* 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.

* 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.
* 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.

Contacts and Locations

Study Contact

Marcia Hodik, RN, BSHS, CCRP

CONTACT

352-273-9000

marcia.hodik@neurosurgery.ufl.edu

Principal Investigator

Ashley Ghiaseddin, MD

PRINCIPAL_INVESTIGATOR

University of Florida

Study Locations (Sites)

University of Florida Health Children's Hospital

Gainesville, Florida, 32608

United States

Collaborators and Investigators

Sponsor: University of Florida

Ashley Ghiaseddin, MD, PRINCIPAL_INVESTIGATOR, University of Florida

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05

Study Completion Date2045-12

Study Record Updates

Study Start Date2025-05

Study Completion Date2045-12

Terms related to this study

Keywords Provided by Researchers

CAR T Cell
Brain Tumor
Brain Cancer
Immunotherapy
Glioblastoma

Additional Relevant MeSH Terms

High-grade Glioma