GD2CART for the Treatment of H3K27M Mutated Diffuse Intrinsic Pontine Glioma or Spinal Diffuse Midline Glioma

Inclusion Criteria

• FOR DOSE ESCALATION: Diagnosis of H3K27M mutated diffuse intrinsic pontine glioma (DIPG)
• FOR DOSE EXPANSION: Diagnosis of H3K27M mutated diffuse intrinsic pontine glioma (DIPG), OR
• FOR DOSE EXPANSION: Diagnosis of spinal H3K27M mutated diffuse midline glioma (DMG)
• At least 6 weeks following completion of standard upfront radiation therapy
• At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy that requires 5 half-lives
• Subjects > 16 years of age: Karnofsky >= 60% OR Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Subjects =< 16 years of age: Lansky scale >= 60%
• Absolute neutrophil count (ANC) >= 1000/uL (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
• Platelet count >= 100,000/uL (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
• Absolute lymphocyte count >= 150/uL (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
• Hemoglobin >= 8 g/dL (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
• Creatinine within institutional norms for age (i.e. =< 2 mg/dL in adults or according to below in children < 18 years) OR creatinine clearance (as estimated by Cockcroft Gault equation) >= 60 mL/min * Age (years); maximum serum creatinine (mg/dL) ** Age =< 5; 0.8 mg/dL ** 5 < age =< 10; 1.0 mg/dL ** > Age 10-18; 1.2 mg/dL ** Age >18; 2.0 mg/dL
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3.0 upper limit of normal (ULN) (grade 1)
• Total bilirubin =< 1.5 mg/dl, except in subjects with Gilbert’s syndrome
• Cardiac ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiography (ECHO), and no clinically significant electrocardiogram (ECG) findings
• Baseline oxygen saturation > 92% on room air
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential)
• Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen or for as long as GD2CART cells are detectable in peripheral blood or CSF
• All subjects >= 18 years of age must be able to give informed consent. For subjects < 18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he/she will be asked to reconsent as an adult

Exclusion Criteria

• Tumor involvement of cerebellar vermis or hemispheres (pontocerebellar peduncles involvement is acceptable), thalamic lesions, or supratentoral lesions
• Clinically significant swallowing dysfunction or prominent dysphagia, as determined by the clinical investigator
• Current systemic corticosteroid therapy
• Prior CAR therapy
• Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable
• Ongoing infection with: * Human immunodeficiency virus (HIV), * Hepatitis B (hepatitis B surface antigen [HBsAg] positive) or * Hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
• Clinically significant systemic illness or medical condition (e.g. significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements
• Women who are pregnant or breastfeeding
• In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
• Known sensitivity or allergy to any agents/reagents used in this study
• Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years