FIERCe: FOLR1 Immune Effector Cell Therapy Against Advanced Osteosarcoma
Fred Hutchinson Cancer Center
Summary
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.
Description
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 ha…
Eligibility
- Age range
- 1–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 * Must have at least one of the following in the 6 months prior to trial consent: * New site of measurable disease by radiographic imaging or histologic confirmation * New site of evaluable disease by radiographic imaging or histologic confirmation * Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a minimum absolute increase of 5 mm in longe…
Interventions
- BiologicalFH FOLR1 ST CAR T-cells
Given IV
- ProcedureLeukapheresis
Undergo leukapheresis
- DrugFludarabine
Given IV
- DrugCyclophosphamide
Given IV
- ProcedureEchocardiography Test
Undergo echocardiography
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- ProcedureBiospecimen Collection
Undergo blood sample collection
Location
- Fred Hutch/University of Washington/Seattle Children's Cancer ConsortiumSeattle, Washington