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.
OUTLINE: This is a dose-escalation study of FH-FOLR1 ST CAR T cells. Patients undergo leukapheresis for manufacturing of the FH-FOLR1 ST CAR T cell product on study. Patients receive lymphodepleting therapy with fludarabine intravenously (IV) on days -5 to -2 and cyclophosphamide IV on days -3 to -2. Patients receive FH-FOLR1 ST CAR T cells IV on day 0, 1 or 2 in the absence of unacceptable toxicity. Patients also undergo blood sample collection, and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) throughout the study. Additionally, patients have the option to undergo tumor biopsy on study. Patients will be monitored closely for at least 28 days after receiving CAR T cells. After completion of study treatment, patients are followed up at days 1, 7, 14, 21, 28, and 42, months 2, 3, 6, 12, and 24, then every 6 months for 3 years followed by annually for 10 years. Patients with ongoing FH-FOLR1 ST CAR T cell persistence are also followed up in months 4, 5, 7, 8, 9, 10, 11, 15, and 18.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given IV
Undergo leukapheresis
Given IV
Given IV
Undergo echocardiography
Undergo MUGA
Undergo blood sample collection
Undergo CT
Undergo MRI
Undergo PET
Undergo tumor biopsy
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
Seattle, Washington, United States
RECRUITINGIncidence of treatment-related unexpected grade 3 or higher toxicity
Time frame: Up to 28 days post infusion
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.
Time frame: Up to 28 days post infusion
Progression free survival
Time frame: From initiation of protocol treatment to disease progression or death of any cause, assessed up to 1 year post infusion
Overall survival
Time frame: From initiation of protocol treatment to death of any cause, assessed up to 1 year post infusion
Overall response rate (ORR)
Will be defined as complete response and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Time frame: Up to 1 year post infusion
Stable disease (SD) rate
Will be evaluated using RECIST 1.1 criteria.
Time frame: Up to 1 year post infusion
Clinical benefit rate
Will be defined as ORR plus SD by RECIST 1.1 criteria.
Time frame: Up to 1 year post infusion
Time to Response (TTR)
For participants with a response (RECIST 1.1) the TTR will be assessed from time of FH-FOLR1 ST CAR T administration to time of first documented response (partial response \[PR\] or better).
Time frame: Up to 1 year post infusion
Duration of Response (DoR)
For participants with a response, the DoR will be assessed from time of first documented response (PR or better) to time of confirmed disease progression (deaths from other causes will be censored).
Time frame: Up to 1 year post infusion
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