AzTrials
AzTrials

Advanced OsteosarcomaPhase 1NCT07227571

Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial

A Phase 1 study testing FH FOLR1 ST CAR T-cells, Leukapheresis and Fludarabine in people with Advanced Osteosarcoma and Recurrent Osteosarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 1 year to 75 years
What is being tested?
FH FOLR1 ST CAR T-cells, Leukapheresis and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
16 Jan 2026to 31 Jan 2044
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 41Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Fred Hutch Immunotherapy Intake contact

206-606-4668

immunotherapy@fredhutch.org

Seattle Children's Hospital Immunotherapy Intake contact

immunotherapy@seattlechildrens.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

    Seattle, Washington, 98109

    Fred Hutch Immunotherapy Intake, 206-606-4668, immunotherapy@fredhutch.org

    Seattle Children's Hospital Immunotherapy Intake, immunotherapy@seattlechildrens.org

    Recruiting

Other trials in United States

About this study

Official title: FIERCe: FOLR1 Immune Effector Cell Therapy Against Advanced Osteosarcoma

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.

Read the detailed 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 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.

Being tested
FH FOLR1 ST CAR T-cells, Leukapheresis, Fludarabine, Cyclophosphamide, Echocardiography Test
Keywords
Bones and Joints
Medical subject headings
Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FH FOLR1 ST CAR T-cellsBiological

    Also called Anti-FOLR1 CAR-T Cells, FH-FOLR1 CAR T Cells

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

    Undergo leukapheresis

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar, Revimmune, Cycloblastin

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC

    Undergo echocardiography

  • Multigated Acquisition ScanProcedure or surgery

    Also called MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide ventriculography

    Undergo MUGA

  • Biospecimen CollectionProcedure or surgery

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CT, CT Scan, CAT Scan, Computed Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called MRI

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called PET, PET Scan

    Undergo PET

  • Biopsy ProcedureProcedure or surgery

    Also called Bx

    Undergo tumor biopsy

Study groups in NCT07227571
Study groupRoleWhat they receive
Treatment (FH-FOLR1 ST CAR T cells)ExperimentalPatients undergo leukapheresis for manufacturing of the FH-FOLR1 ST CAR T cell product on study. Patients will receive lymphodepleting therapy with fludarabine 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 echocardiography or multigated acquisition scan (MUGA), blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may have the option of undergoing tumor biopsy on study.
Receives: Biological: FH FOLR1 ST CAR T-cells; Procedure: Leukapheresis; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biopsy Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of treatment-related unexpected grade 3 or higher toxicity

    Measured: Up to 28 days post infusion

  2. 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.

    Measured: Up to 28 days post infusion

Secondary outcomes (7)

  1. Progression free survival

    Measured: From initiation of protocol treatment to disease progression or death of any cause, assessed up to 1 year post infusion

  2. Overall survival

    Measured: From initiation of protocol treatment to death of any cause, assessed up to 1 year post infusion

  3. Overall response rate (ORR)

    Will be defined as complete response and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

    Measured: Up to 1 year post infusion

  4. Stable disease (SD) rate

    Will be evaluated using RECIST 1.1 criteria.

    Measured: Up to 1 year post infusion

  5. Clinical benefit rate

    Will be defined as ORR plus SD by RECIST 1.1 criteria.

    Measured: Up to 1 year post infusion

  6. 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).

    Measured: Up to 1 year post infusion

  7. 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).

    Measured: Up to 1 year post infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2025
  2. Study start16 Jan 2026
  3. Primary completion31 Jan 2029 (estimated)
  4. Study completion31 Jan 2044 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07227571
Sponsor's protocol ID
RG1125765
Other IDs
NCI-2025-08064, FH20941
Status last verified
Aug 2026
First submitted
10 Nov 2025
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FH FOLR1 ST CAR T-cells, Leukapheresis and Fludarabine in people with Advanced Osteosarcoma and Recurrent Osteosarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Fred Hutch Immunotherapy Intake (206-606-4668, immunotherapy@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-related unexpected grade 3 or higher toxicity (time frame: Up to 28 days post infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07227571.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in