转基因 T 细胞治疗复发性或难治性恶性神经胶质瘤患者

Inclusion Criteria:

• SCREENING INCLUSION CRITERIA

• Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG) after completing standard therapy

• Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial radiation therapy

• Karnofsky performance status (KPS) >= 60%

• Life expectancy > 4 weeks

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

• City of Hope (COH) Clinical Pathology confirms IL13R alpha 2+ tumor expression by immunohistochemistry (>= 20%, 1+)

• All research participants must have the ability to understand and the willingness to sign a written informed consent

• ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION

• Research participant must not require more than 2 mg three times daily (TID) of dexamethasone on the day of PBMC collection.

• Research participant must have appropriate venous access

• At least 2 weeks must have elapsed since the research participant received his/her last dose of prior chemotherapy or radiation

• ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT

• Creatinine < 1.6 mg/dL

• White blood cell (WBC) > 2,000/dl or

• Absolute neutrophil count (ANC) > 1,000

• Platelets >= 100,000/dl

• International normalized ratio (INR) < 1.3

• Bilirubin < 1.5 mg/dL

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limits of normal

• An interval of at least 12 weeks must have elapsed since the completion of initial radiation therapy

• Wash-out requirements (standard or investigational):

  • At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen
  • At least 23 days since the completion of Temodar and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment

• ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH CAR T CELL INFUSION

• Research participant has a released cryopreserved T cell product

• Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive

• Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias

• Research participant does not have a fever exceeding 38.5° Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis

• Research participant serum total bilirubin does not exceed 2 x normal limit

• Research participant transaminases does not exceed 2 x normal limit

• Research participant serum creatinine =< 1.8 mg/dL

• Research participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell dose

• Research participant platelet count must be >= 100,000; however, if platelet level is between 75,000-99,000, then T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is >= 100,000

• Research participants must not require more than 2 mg TID of dexamethasone during T cell therapy

Exclusion Criteria:

• SCREENING EXCLUSION CRITERIA
• Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
• Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
• Research participant requires dialysis
• Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
• Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
• Research participants with any other active malignancies
• Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
• Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• Research participants who have confirmed human immunodeficiency virus (HIV) within 4 weeks of screening