Genetically Engineered Cells (SC-CAR.GPC3xIL15.21 T Cells) for the Treatment of Pediatric and Adolescent/Young Adult Patients with GPC3-Positive Solid Cancers, IMPACT Trial

Inclusion Criteria

• PROCUREMENT: Diagnosis of GPC3-positive solid tumors (as determined by immunohistochemistry with an extent score of >= grade 2 [> 25% positive tumor cells] and an intensity score of >= 2 [scale 0-4]) * GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Seattle Children’s Hospital, Department of Pathology for all patients to meet procurement eligibility. All patients will send at least 5 unstained slides
• PROCUREMENT: Age >= 1 year and =< 26 years
• PROCUREMENT: Lansky or Karnofsky score >= 60%
• PROCUREMENT: Life expectancy >= 16 weeks
• PROCUREMENT: Barcelona Clinic Liver Cancer stage A, B or C (for patients with hepatocellular carcinoma only)
• PROCUREMENT: Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only)
• TREATMENT: Age >= 1 year and =< 26 years
• TREATMENT: Lansky or Karnofsky score >= 60%
• TREATMENT: Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only)
• TREATMENT: Barcelona Clinic Liver Cancer stage A, B or C (for patients with hepatocellular carcinoma only)
• TREATMENT: Creatinine clearance as estimated by Cockcroft Gault or Schwartz >= 60 ml/min
• TREATMENT: Total bilirubin < 3 times upper limit of normal (ULN) for age
• TREATMENT: International normalized ratio (INR) =< 1.7 (for patients with hepatocellular carcinoma only)
• TREATMENT: Absolute neutrophil count >= 750/ul
• TREATMENT: Platelet count >= 75,000/ul (needs to be confirmed prior to treatment whether with or without transfusion)
• TREATMENT: Hemoglobin (Hgb) >= 8.0 g/dl (needs to be confirmed prior to treatment whether with or without transfusion)
• TREATMENT: Pulse oximetry >= 92% on room air
• TREATMENT: Incurable disease after treatment with up-front therapy (patients who have relapsed disease despite a standard of care salvage therapy)
• TREATMENT: Wash out period, such that patient has recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study, and returned to their clinical baseline, as determined by history and physical exam
• TREATMENT: If subject is of child-bearing or child-fathering potential, must agree to use highly effective contraception from the time of initial consent through 12 months following the infusion of investigational product on this trial
• TREATMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria

• PROCUREMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
• PROCUREMENT: History of organ transplantation
• PROCUREMENT: Known HIV positivity
• PROCUREMENT: Active bacterial, fungal, or viral infection (except hepatitis B or hepatitis C virus infections)
• TREATMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
• TREATMENT: History of organ transplantation
• TREATMENT: Known HIV positivity
• TREATMENT: Active autoimmune or inflammatory disorder
• TREATMENT: Live vaccines within 30 days prior to enrollment
• TREATMENT: Pregnancy or lactation
• TREATMENT: Uncontrolled infection
• TREATMENT: Active bacterial, fungal or viral infection (except hepatitis B [hepatitis B virus (HBV) patients with active disease who meet the criteria for anti-HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy] or hepatitis C virus infections [should have completed curative antiviral treatment with hepatitis C virus (HCV) viral load below the limit of quantification])
• TREATMENT: Systemic steroid treatment (>= 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24 hours prior to CAR T cell infusion)
• TREATMENT: Congestive heart failure (as defined by New York Heart Association functional classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis
• TREATMENT: Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow-up period, required if CAR T cell therapy is administered
• TREATMENT: Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol