This phase I trial tests the safety, side effects, and best dose of FH-FOLR1 ST chimeric antigen receptor (CAR) T cells and how well they work in treating patients with osteosarcoma that recurred or spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has not responded to previous treatment (refractory) or has come back after a period of improvement (recurrent)/is growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they attack tumor cells. T cells are taken from a patient's blood through a process called apheresis. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells, such as FOLR1, is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by an intravenous infusion. Chemotherapy drugs, such as fludarabine and cyclophosphamide, are given to a patient before the manufactured FH-FOLR1 ST CAR T cells to make room for the CAR T cells in the blood and to enhance the CAR T cell activity in the patient. FH-FOLR1 ST CAR T cells may be safe, tolerable, and/or effective in treating patients with advanced refractory or recurrent/progressive osteosarcoma.
Age 1-75 years at the time of enrollment
Tissue confirmation of osteosarcoma diagnosis
Must have received an anthracycline-based regimen or been deemed ineligible to receive this therapy
New site of measurable disease by radiographic imaging or histologic confirmation
Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI
Corticosteroid therapy at a dose equivalent of > 15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable. For participants weighing ≤ 30 kg, systemic steroids ≥ 0.5 mg prednisone equivalent/kg/day
Concurrent use of other investigational anti-cancer agents
Active uncontrolled infection: HIV positive participants on highly active antiretroviral therapy (HAART) with a CD4 count > 500 cells/mm^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
Single group
FH FOLR1 ST CAR T-cells
Biological/VaccineGiven IV
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Fludarabine
DrugGiven IV
Cyclophosphamide
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo echocardiography
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Incidence of treatment-related unexpected grade 3 or higher toxicity
Maximum tolerated dose/recommended phase 2 dose
Will be defined as the highest T cell dose from among those tested for which the dose limiting toxicity (DLT) rate is closest to 28% and that at least 4 participants have been evaluated at that level. All observed DLT outcomes for toxicity-evaluable participants will be tabulated by dose level. Will employ a novel Bayesian optimal interval design.
Progression free survival
Overall survival
Overall response rate (ORR)
Will be defined as complete response and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Stable disease (SD) rate
Will be evaluated using RECIST 1.1 criteria.
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Fred Hutchinson Cancer Center
Lead sponsor
Washington Research Foundation
Collaborator
