Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

INCLUSION CRITERIA \*a previously collected, autologous leukapheresis product can be used for T cell production Collection and manufacturing eligibility * Age ≤ 21 years old * B7-H3+ sarcoma; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using any previously obtained biopsy; a tumor is considered B7-H3 positive with a H score greater than or equal to 100 * Osteosarcoma * Ewing Sarcoma * Rhabdomyosarcoma Non-rhabdomyosarcoma soft tissue sarcomas * Evidence of relapsed (cancer that has completely responded \[i.e., no evidence of disease using standard imaging modalities\] to first-line therapy but has recurred for the first or subsequent time); or refractory (cancer that does not respond completely to treatment; cancer may be resistant at the beginning or may become resistant during treatment) disease after standard first-line therapy * Evaluable disease with presence of at least one lesion amenable to hypofractionated radiation therapy * For dose expansion cohort: participants must also have additional evaluable disease beyond planned radiation field * Estimated life expectancy of \> 12 weeks * Karnofsky or Lansky (age-dependent) performance score ≥ 60 * Participants with mobility limitations due to prior surgical intervention (i.e., amputation) but who are up in wheelchair or with other assistive devices will be considered ambulatory for the purpose of performance score determination * 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 * Participants must be eligible to undergo autologous apheresis or have an available previously collected autologous apheresis product Treatment eligibility * Age ≤ 21 years old at the time of manufacturing * B7-H3+ sarcoma * Evidence of relapsed or refractory disease after standard first-line therapy * Evaluable disease with the presence of at least one lesion amenable to hypofractionated radiation therapy • For dose expansion cohort: participants must also have additional evaluable disease beyond the planned radiation field * Estimated life expectancy of \> 8 weeks * Karnofsky or Lansky (age-dependent) performance score ≥ 60 • Participants with mobility limitations due to prior surgical intervention (i.e., amputation) but who are up in wheelchair or with other assistive device will be considered ambulatory for purpose of performance score determination. * Adequate cardiac function defined by echocardiogram with left ventricular ejection fraction ≥ 50% * Adequate renal function as defined by not exceeding the maximum serum creatinine listed below by age: * 1 to \<2 years: 0.6 * 2 to \<6 years: 0.8 * 6 to \<10 years: 1 * 10 to \<13 years: 1.2 * 13 to \<16 years: male 1.5, female 1.4 * ≥ 16 years: male 1.7, female 1.4 * Adequate pulmonary function defined as pulse oximetry ≥ 92% on room air * 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/μL (can be transfused) * Absolute neutrophil count (ANC) ≥ 1000/μL * 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 contraception until 3 months after T cell infusion EXCLUSION CRITERIA Collection and manufacturing eligibility * Known primary immunodeficiency * Known HIV positivity * Severe, uncontrolled intercurrent bacterial, viral, or fungal infection * Known active malignancy other than the B7-H3+ sarcoma being treated on study * Rapidly progressive disease (as assessed by the study PIs, with consideration for proximity to critical structures) * Presence of intracranial or spinal cord disease * Known underlying medical condition(s) for which, in the investigator's opinion, participation in this trial would not be in the best interest of the participant (e.g., compromises the health of the subject) or that could prevent, limit, or confound protocol assessments * Known severe hypersensitivity to corn starch or hydroxyethyl starch Treatment eligibility * Known primary immunodeficiency * Known HIV positivity * Severe, uncontrolled intercurrent bacterial, viral, or fungal infection * Known active malignancy other than the B7-H3+ sarcoma being treated on study * Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, \< 7 days prior to CAR T cell infusion * Receiving systemic therapy \< 14 days prior to start of protocol therapy, which will interfere with the activity of the CAR product (in the opinion of the study PIs) * Received radiation therapy within the 4 weeks prior to start of protocol therapy * Rapidly progressive disease (as assessed by the study PIs, with consideration for proximity to critical structures) * Presence of intracranial or spinal cord disease * Known underlying medical condition(s) for which, in the investigator's opinion, participation in this trial would not be in the best interest of the participant (e.g., compromises the health of the subject) or that could prevent, limit, or confound protocol assessments * Known severe hypersensitivity to corn starch or hydroxyethyl starch