B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Eligibility Criteria

• * Age ≤21 years old
• * B7-H3+ solid tumor with measurable disease; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor is considered B7-H3 positive with an H-score ≥100
• * Estimated life expectancy of \>12 weeks
• * Karnofsky or Lansky (age-dependent) performance score ≥50
• * For females of child bearing age:
• * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
• * Not lactating with intent to breastfeed
• * Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis
• * Known primary immunodeficiency
• * Known HIV positivity
• * Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
• * History of hypersensitivity reactions to murine protein-containing products
• * Rapidly progressive disease (in the opinion of the study PIs)
• * Age ≤21 years old
• * B7-H3+ solid tumor with measurable disease
• * Evidence of relapsed or refractory disease after standard first-line therapy
• * Estimated life expectancy of \>8 weeks
• * Karnofsky or Lansky (age-dependent) performance score≥50
• * Echocardiogram with a ventricular ejection fraction
• * \>40%; or shortening fraction ≥25%
• * Adequate renal function defined as creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age)
• * Adequate pulmonary function defined as pulse oximetry ≥92% on room air or forced vital capacity (FVC) ≥50% of predicted value
• * Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
• * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age
• * Hemoglobin≥ 7g/dL (can be transfused)
• * Platelet count \>50,000/uL (can be transfused)
• * Absolute neutrophil count (ANC) ≥ 1000/uL
• * Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
• * For females of child bearing age:
• * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
• * Not lactating with intent to breastfeed
• * If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom.
• * Available autologous transduced T-cell product that has met GMP release criteria
• * Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products
• * Known primary immunodeficiency
• * History of HIV infection
• * Severe, uncontrolled intercurrent bacterial, viral or fungal infection
• * History of hypersensitivity reactions to murine protein-containing products
• * Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion
• * Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs).
• * Rapidly progressing disease (in the opinion of the study PIs)