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About
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
Full 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, PBMCs will be collected through peripheral venipuncture. After tumor CD70 status is confirmed, the 8R-70CAR T cell production will start.
4 weeks (+/- 1) post completion of radiation, pediatric patients, based on institutional policy, will initiate adjuvant chemo with dose-intensified TMZ 75-100 mg/m2/day x 21 days for up to 3 cycles. 8R-70CAR T cells will be administered at day 21-24 of the TMZ cycle as a single intravenous (IV) infusion, or for pediatric patients not receiving adjuvant chemo once 8R-70CAR T cells. Pediatric patients will receive lymphodepletion prior to CAR T cell administration.
Enrollment
Sex
Ages
Volunteers
Inclusion 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.
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
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:
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:
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 criteria
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:
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)
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)
Primary purpose
Allocation
Interventional model
Masking
18 participants in 1 patient group
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Central trial contact
Marcia Hodik, RN, BSHS, CCRP
Data sourced from clinicaltrials.gov
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