FH-FOLR1 ST CAR T Cells for Advanced Osteosarcoma (FIERCe Trial)
This study, called the FIERCe trial, is testing a new treatment called FH-FOLR1 ST CAR T cells for people aged 1 to 75 with advanced osteosarcoma (bone cancer that has spread or come back) that hasn't responded to previous treatments. CAR T-cell therapy involves taking your own immune cells (T cells), modifying them in a lab to better fight cancer, and then giving them back to you. Before receiving the CAR T cells, you will get chemotherapy drugs called fludarabine and cyclophosphamide. The main goals of this study are to find out how safe FH-FOLR1 ST CAR T cells are, what side effects they might cause, and to determine the best dose. The study aims to enroll 30 participants, but its current status is unclear.
- Study design
- This is a dose-escalation study, meaning participants will receive increasing doses of the treatment to find the safest and most effective amount. The study plans to enroll 30 participants.
- What's involved
- You would undergo leukapheresis to collect your T cells, receive chemotherapy (fludarabine and cyclophosphamide), and then receive the FH-FOLR1 ST CAR T cells intravenously. You will also have blood tests, imaging scans (CT, MRI, or PET), and potentially a tumor biopsy.
- Compensation
- Not stated in the trial record.
- Follow-up
- You will be closely monitored for at least 28 days after receiving the CAR T cells. After this, you will have follow-up visits for up to 10 years, with more frequent visits in the first two years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07227571
Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial
Recruiting
PHASE1Ages 1–75InterventionalTreatmentFred Hutchinson Cancer CenterInvestigator-initiated
~30 participants
Updated 2026-02-11 on ClinicalTrials.gov
What's tested:FH FOLR1 ST CAR T-cellsLeukapheresisFludarabineCyclophosphamideEchocardiography TestMultigated Acquisition Scan
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of treatment-related unexpected grade 3 or higher toxicity
Measured over Up to 28 days post infusion
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesWashington1
Study leadership
- Michelle Choe, MD · PRINCIPAL_INVESTIGATOR · Fred Hutch/University of Washington/Seattle Children's Cancer Consortium
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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 longest dimension of existing lesion(s) (previously irradiated lesions may be included)
Persistent measurable disease or fludeoxyglucose F-18 (FDG)-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy, and/or chemotherapy)
All anti-cancer therapy must be discontinued at enrollment/time of apheresis, with the following washout periods observed:
Chemotherapy and biologic agents: ≥ 7 days prior to enrollment
Steroid use: All corticosteroid therapy (unless physiologic replacement dosing and/or topical administration (e.g., inhaled or dermatologic) ≥ 7 days prior to enrollment
Tyrosine kinase inhibitor (TKI) use: ≥ 7 days prior to enrollment
Antitumor antibody therapy (including immune checkpoint inhibitor) must be ≥ 3 half-lives or 30 days, whichever is shorter, from time of enrollment
FOLR1 targeting therapy must be discontinued at least 30 days prior to enrollment
Gene modified cellular therapy: At enrollment, must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR must be at least 60 days from most recent gene modified cell therapy
Washout periods not applicable to patients with apheresis product or usable T cell product available for use at time of enrollment
Potential trial participants should have recovered to grade 1 from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
Ability to understand and willingness to sign a written informed consent document.
Females of child-bearing potential and fertile male participants must be willing to use an effective contraceptive method before, during, and for at least 12 months after the FOLR1 CART cell infusion
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (if treated at adult facility) or Lansky/Karnofsky score ≥ 60 (if treated at pediatric facility). Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
Life expectancy ≥ 8 weeks
Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing
Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Participants with treated brain metastases are eligible if they meet the following criteria:
Follow-up brain imaging taken at screening demonstrates no evidence of progression and that imaging occurs 3 months after central nervous system (CNS)-directed therapy has been completed
No ongoing, symptomatic CNS pathology requiring medical intervention
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) based on age and gender; or estimated creatinine clearance \> 50 mL/min as calculated using the Cockcroft-Gault formula and not dialysis dependent
Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): 0.6 (male), 0.6 (female)
Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female)
Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): 1 (male), 1 (female)
Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female)
Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female)
Age: ≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
Total bilirubin ≤ 3 x ULN or conjugated bilirubin ≤ 2 mg/dL. Participants with suspected Gilbert syndrome may be included if total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN
Pulmonary: ≤ grade 1 dyspnea at rest and arterial oxygen saturation (SaO2) ≥ 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) ≥ 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of ≥ 40% of predicted will be eligible
Left ventricular ejection fraction (LVEF) may be established with echocardiogram or MUGA scan, and left ejection fraction must be ≥ 50% or shortening fraction ≥ 28%
Absolute neutrophil count (ANC) ≥ 500 cells/ mm\^3
Hemoglobin ≥ 8 g/dL
Platelets ≥ 100,000 per mm\^3
Participants receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory
Exclusion
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
Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements
Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI
Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable
Pregnant, possibly pregnant or those expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion
Participants unwilling to provide consent/assent for participation in the study and 15-year follow-up period if CAR T cell therapy is administered
Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
Known allergic reactions to any of the components of study treatments
What this trial measures
- Incidence of treatment-related unexpected grade 3 or higher toxicityUp to 28 days post infusion
- Maximum tolerated dose/recommended phase 2 doseUp to 28 days post infusion
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.