Fluorescein-Specific CAR-T Cells and UB-TT170 (Formerly EC17) in Treating Patients with Recurrent or Refractory Osteosarcoma

Inclusion Criteria

• Male and female subjects age >= 15 and =< 30 years.
• Evidence of refractory or recurrent/progressive osteosarcoma that has failed first line therapy for osteosarcoma per National Comprehensive Cancer Network (NCCN) or upfront Children’s Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following): * New site of measurable disease by radiographic imaging or histologic confirmation * New site of evaluable disease by radiographic imaging (including fludeoxyglucose (FDG)-positron emission tomography [PET]) or histologic confirmation * Greater than 20% increase in at least one tumor dimension documented by computed tomography (CT)/magnetic resonance imaging (MRI), AND a minimum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included) * Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy).
• Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing
• Life expectancy >= 8 weeks.
• Lansky or Karnofsky score >= 50. Subjects who are unable to walk because of paralysis or surgery, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status.
• Subject has discontinued all anti-cancer agents and radiotherapy and, in the opinion of an investigator, has fully recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy.
• All cytotoxic chemotherapy must be discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01).
• All biologic therapy must be discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01).
• The last dose of anti-tumor antibody therapy (including immune check-point inhibitor) must be >= 3 half-lives or 30 days, whichever is shorter, from the time of enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01).
• In subjects who have received genetically modified cell therapy, it must be at least 30 days from most recent cell infusion prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01).
• All systemic corticosteroid therapy (unless physiologic replacement dosing) has been discontinued >= 7 days prior to enrollment (this does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01). Glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency and/or topical administration (e.g., inhaled or dermatologic) is allowed
• Absolute lymphocyte count (ALC) >= 100 cells/uL. * This does not apply to subjects with apheresis product or usable T cell product available for use in ENLIGHTen-01.
• Absolute neutrophil count (ANC) >= 500 cells/uL.
• Hemoglobin > 8 g/dL. * Subjects receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory.
• Platelets > 100,000/uL. * Subjects receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory.
• Subject has adequate renal function defined as a serum creatinine =< upper limit of normal (ULN) based on gender (1.7 mg/dL for males and 1.4 mg/dL for females) * Serum creatinine upper limit of normal values (in mg/dL) ** 1 to < 2 years, Male 0.6, Female 0.6 ** 2 to < 6 years, Male 0.8, Female 0.8 ** 6 to < 10 years, Male 1.0, Female 1.0 ** 10 to < 13 years, Male 1.2, Female 1.2 ** 13 to < 16 years, Male 1.5, Female 1.4 ** >= 16 years, Male 1.7, Female 1.4
• Total bilirubin: =< 3 x upper limit of normal (ULN) for age OR direct bilirubin =< 2 mg/dl.
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 times the ULN, AND
• Aspartate aminotransferase (AST) =< 5 times the ULN.
• Subject has adequate cardiac function, defined as shortening fraction >= 28% or ejection fraction >= 50% by echocardiogram.
• Subject has adequate respiratory function, defined as an oxygen saturation >= 90% on room air without supplemental oxygen or ventilation, and no dyspnea at rest.
• Negative virology tests within 3 months prior to enrollment: * Negative human immunodeficiency virus (HIV) antigen and antibody, AND * Negative hepatitis B surface antigen, AND * Negative hepatitis C antibody (if hepatitis C antibody is positive, subject must have a subsequent negative hepatitis C quantitative polymerase chain reaction [qPCR]).
• Subjects of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the final infusion of investigational product (T cell or UB-TT170).

Exclusion Criteria

• Subject has an active malignancy (including primary central nervous system [CNS] malignancy) other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed).
• Subject has ongoing, symptomatic CNS pathology requiring medical intervention, including paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder (subjects with non-febrile seizure disorder controlled on anti-epileptic medication and without seizure activity within 3 months are eligible)
• Receiving external beam radiation therapy (there is no wash-out period, however subjects may not be receiving therapy at the time of enrollment)
• Subject has presence of active severe infection, defined as: * Positive blood culture within 48 hours of enrollment, AND/OR * Fever >= 38.2 degrees Celsius, AND clinical signs of infection within 48 hours of enrollment
• Subject has primary immunodeficiency syndrome.
• Subject is pregnant or breastfeeding.
• Subject and/or authorized legal representative are unwilling to provide consent/assent for study participation including participation in the 15-year follow-up period that is required if CAR T cell therapy is administered.
• Subject has presence of any condition that, in the opinion of an investigator, would prohibit the subject from undergoing treatment under this protocol.