Locoregional Administration of Genetically Engineered Cells (EGFR/IL13Rα2 Pool-CAR T Cells) for the Treatment of Recurrent or Progressive High-Grade Gliomas

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/biopsy/catheter placement and CAR T cell infusion only after the translated main consent form is signed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study PI approval
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 70%, Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy ≥ 4 weeks
• Participant has a prior histologically-confirmed diagnosis of a glioblastoma (IDH-wildtype) or grade 4 IDH-mutant astrocytoma, or has a prior histologically-confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 4 IDH-mutant astrocytoma
• Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy (such as temozolomide with or without Optune device), and ≥ 12 weeks after completion of front-line radiation therapy
• COH Clinical Pathology assessment at the initial tumor presentation or recurrent disease * IL13Rα2+ tumor expression by immunohistochemistry (H-score ≥ 20), and * EGFR gene altered by next generation sequencing (NGS) or fluorescence in situ hybridization (FISH) analysis (archival tissue testing results may be acceptable for enrollment)
• No known contraindications to leukapheresis, steroids, imaging studies, or tocilizumab
• White blood cell (WBC) > 2000 /dl (or absolute neutrophil count [ANC] ≥ 1,000/mm^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Platelets ≥ 75,000/mm^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Hemoglobin ≥ 9g/dl (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Total bilirubin ≤ 1.5x upper limit of normal (ULN) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Aspartate aminotransferase (AST) ≤ 2.5x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Alanine aminotransferase (ALT) ≤ 2.5x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Serum creatinine ≤ 1.6 mg/dL (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Oxygen (O2) saturation ≥ 95% on room air (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Seronegative for HIV antigen/antibody (Ag/Ab) combination (combo), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Note: Meets other institutional and federal requirements for infectious disease titer
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 14 days prior to leukapheresis unless otherwise stated) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
• CRITERIA TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION: Research participant must not require more than 6 mg daily of dexamethasone on the day of PBMC collection
• CRITERIA TO PROCEED WITH PBMC COLLECTION: Research participant must have appropriate venous access or be willing to undergo central catheter line placement
• CRITERIA TO PROCEED WITH PBMC COLLECTION: At least 2 weeks must have elapsed since the research participant received his/her last dose of prior targeted agents, chemotherapy, or radiation
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Research participant has signed the treatment consent
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: ECOG ≤ 2 or KPS ≥ 60%
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Second-line radiation therapy (post-leukapheresis) completed at least 4 weeks prior to surgical resection/catheter placement
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Wash-out requirements: * At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen * At least 23 days since the completion of temozolomide and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen. If a participant’s most recent treatment was with a targeted agent only, and they have recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Creatinine < 1.6 mg/dL
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: WBC > 2,000/dl (or ANC > 1,000)
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Platelets ≥ 100,000/dl
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Hemoglobin (Hb) ≥ 9g/dl
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: International normalized ratio (INR) < 1.3
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: Bilirubin ≤ 1.5x ULN
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: ALT ≤ 2.5 X upper limits of normal
• CRITERIA TO PROCEED WITH SURGICAL RESECTION/BIOPSY/CATHETER PLACEMENT: AST ≤ 2.5 X upper limits of normal
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participants will be evaluated for eligibility to proceed with CAR T cell infusion no more than 1 day prior to CAR T cell infusion
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant has a signed treatment consent on file
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant has a released cryopreserved CAR T cell product
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Participant has completed required catheter placement(s)
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Physical exam including vital signs (pulse rate, temperature, respiratory rate, blood pressure)
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: ECOG ≤ 2 or KPS ≥ 60%
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Complete blood count, differential, ANC
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Chemistry panel (CMP)
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant does not require supplemental oxygen to keep saturation ≥ 95% or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant platelet count must be ≥ 100,000. However, if platelet level is between 75,000-99,000, then CAR T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is ≥ 100,000
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant hemoglobin ≥ 9g/dl
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Neurologic: Research participant does not have uncontrolled seizure activity following surgery prior to starting the first CAR T cell dose
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant serum creatinine ≤ 1.6 mg/dL
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: AST and ALT do not exceed ≤ 2.5x ULN
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Research participant’s serum total bilirubin ≤ 1.5x ULN
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: No untreated or active systemic infection
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: Steroid dependency: Research participants may receive high-dose dexamethasone while on CAR T treatment but must not require more than 12 mg daily of dexamethasone within 24 hours prior to each CAR T cell infusion
• CRITERIA TO PROCEED WITH CAR T CELL INFUSION: 35cc peripheral blood will be collected for correlative studies (drawn prior to CAR T cell infusion)

Exclusion Criteria

• Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded
• Participant has not yet recovered from toxicities of prior therapy
• Participant has received any live vaccine within 30 days prior to enrollment
• Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Clinically significant uncontrolled illness
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Active infection requiring intravenous (IV) antibiotics (e.g., minor scalp infection is not an exclusion)
• Known history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Other active malignancy. Note: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator’s judgment, contraindicate the patient’s participation in the clinical study due to safety concerns with clinical study procedures
• Adults lacking capacity to consent due to cognitive impairment are excluded from participation. This includes prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)