Donor Immune Cells (TGFBi NK cells) for the Treatment of Recurrent, Progressive or Refractory Malignant Brain Tumors in Children and Young Adults

Inclusion Criteria

• Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
• Recurrent, refractory, or progressive malignant CNS tumor * Patients with a histologically confirmed diagnosis of a CNS tumor that is recurrent, progressive, or refractory with the exception of diffuse midline gliomas (DMG) or diffuse intrinsic pontine gliomas (DIPG). All tumors must have histologic verification at either the time of diagnosis or recurrence. * Patients should be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral or a programable VP shunt. * Measurable residual tumor after surgery is not required for study entry. * Resection cavity needs to be at least 2 cm x 2 cm in two dimensions on imaging for patients deemed as candidates for an intratumoral infusion via an Ommaya reservoir.
• Lansky score of 50 or greater if ≤ 16 years of age or a Karnofsky score of 50 or greater if > 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Hemoglobin (Hgb) ≥ 9 gm/dL (within 21 days of NK cell administration).
• Absolute neutrophil count (ANC) ≥ 750 cells/microliter (within 21 days of NK cell administration).
• Platelet count of ≥ 75,000 cells/microliter (within 21 days of NK cell administration).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase < 3 times upper limit of normal (ULN) (prior to NK cell).
• Bilirubin < 1.5 times ULN (prior to NK cell).
• Creatinine < 1.5 times ULN (prior to NK cell).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70ml/min/1.73 m^2 OR serum creatinine based on age/gender.
• Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) < 1.5 x ULN.
• Patients of child-bearing potential 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.
• Patients with seizure disorder may be enrolled if seizures are well controlled. * Signs and symptoms of neurologic deficit must be stable for ≥ 1 week prior to enrollment.
• Chemotherapy * All patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days of nitrosourea. * For patients who have received prior bevacizumab, at least 6 weeks must have elapsed prior to enrollment.
• Biologic or investigational agent (anti-neoplastic, non-myelosuppressive): * Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 14 days prior to study enrollment. * For agents with known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * At least 12 weeks since the completion of any immunotherapies or cell therapies.
• Radiation therapy * Focal radiation therapy > 6 weeks prior to enrollment. * Craniospinal irradiation > 12 weeks.
• Stem cell transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft versus (vs.) host disease. * ≥ 3 months since autologous stem cell transplant prior to enrollment.
• Growth factors * Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim or erythropoietin). * 2 weeks must have elapsed if patients received long-acting formulations.
• Corticosteroids * Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.

Exclusion Criteria

• Patients with intra- or extra-CNS metastasis or multi-focal disease.
• Patients with diffuse midline gliomas or diffuse intrinsic pontine gliomas (primary or recurrent).
• Pregnant or lactating patients.
• Participants who are receiving any other investigational agents.
• Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
• Any medical condition that precludes surgery.
• Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.
• Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued > 1 week prior to NK cell infusion then the subject may be eligible following consultation with the principal investigator (PI).
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject’s ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.