HER2-Specific CAR T Cell Immunotherapy in Treating Patients with Recurrent or Refractory Central Nervous System Tumors

Inclusion Criteria

• First 2 subjects enrolled: subjects age >= 15 and =< 26 years (this requirement has been met as of 2/25/2019); subsequent subjects: subjects age >= 1 and =< 26 years
• Histologically diagnosed HER2-positive CNS tumor. HER2 testing must have been performed in an accredited facility with either a Food and Drug Administration (FDA)-approved test, or a test that meets accreditation standards. Test results will be confirmed per Sponsor’s standard operating procedure (SOP).
• Evidence of refractory or recurrent CNS disease for which there is no standard therapy, defined by either of the following: * New site or sites of measurable or evaluable disease by radiographic imaging or histologic confirmation following completion of standard of care first-line therapy for which curative salvage therapy is not available or amenable, OR * Measurable or evaluable disease that persists following completion of standard of care first-line therapy for which curative salvage therapy is not available or amenable.
• Able to tolerate an apheresis or already has an apheresis product available for use in manufacturing.
• CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy delivered as specified for BrainChild-01.
• Life expectancy >= 8 weeks.
• Lansky or Karnofsky score >= 60. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status.
• If subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of CAR T cells, subject must discontinue all anti-cancer agents and radiotherapy and, in the opinion of the investigator, have fully recovered from significant acute toxic effects of the following: * Chemotherapy/biologic therapy: All cytotoxic chemotherapy/biologic therapy must be discontinued >= 7 days prior to enrollment. * Antibody therapy: The last dose of anti-tumor antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment. Bevacizumab will be considered biologic therapy. * Cellular therapy: Must be at least 30 days from most recent cell infusion prior to enrollment. * Steroid use: All systemically administered (i.e. subcutaneous, intramuscular, oral [PO] or intravenous [IV]) corticosteroid therapy (unless physiologic replacement dosing) must be stable or decreasing for 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5 mg/m^2 /day ongoing at enrollment. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.
• Absolute lymphocyte count (ALC) >= 500 cells/uL. * Value not required to be met if subject has previously obtained apheresis product acceptable and available for manufacturing of CAR T cells
• Absolute neutrophil count (ANC) >= 500 cells/uL.
• Hemoglobin >= 9 g/dL * Subjects receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory.
• Platelets >= 100,000/uL * Subjects receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory.
• Serum creatinine =< upper limit of normal (ULN) based on age and gender: * 1 to < 2 years (yrs) (male 0.6 mg/dL, female 0.6 mg/dL) * 2 to < 6 yrs (male 0.8 mg/dL, female 0.8 mg/dL ) * 6 to < 10 yrs (male 1 mg/dL, female 1 mg/dL) * 10 to < 13 yrs (male 1.2 mg/dL, female 1.2 mg/dL) * 13 to < 16 yrs (male 1.5 mg/dL, female 1.4 mg/dL) * >= 16 yrs (male 1.7 mg/dL, female 1.4 mg/dL).
• Total bilirubin: < 3 x ULN for age OR conjugated bilirubin < 2 mg/dL.
• Oxygen saturation >= 90% on room air without supplemental oxygen or mechanical ventilation, AND no dyspnea at rest
• Signs and symptoms of neurologic deficit must be stable for >= 1 week prior to enrollment, AND =< two anti-epileptic agents are required to control seizure activity, AND no clinically evident encephalopathy present.
• Virology negative within 3 months prior to enrollment, to include all of the following: * Human immunodeficiency virus (HIV) antigen & antibody, AND * Hepatitis B surface antigen, AND * Hepatitis C antibody OR if antibody positive, hepatitis C polymerase chain reaction (PCR) is negative.
• Subjects of childbearing/fathering potential must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the last T cell infusion.

Exclusion Criteria

• Diagnosis of classic diffuse intrinsic pontine glioma (DIPG).
• Presence of >= grade 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention.
• Presence of primary immunodeficiency/bone marrow failure syndrome.
• Presence of clinical and/or radiographic evidence of impending herniation.
• Presence of active malignancy other than the CNS tumor under study.
• Presence of active severe infection, defined as: * Positive blood culture within 48 hours of enrollment, OR * Fever >= 38.3 degrees Celsius (°C) AND clinical signs of infection within 48 hours of enrollment.
• Receiving any anti-cancer agents or chemotherapy.
• Pregnant or breastfeeding.
• Subject and/or authorized legal representative unwilling to provide consent/assent for participation in the 15 year follow-up period, required if CAR T cell therapy is administered.
• Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.