CAR T-Cell Therapy for Bone Cancer

Overseen By Seattle Children's Hospital Immunotherapy Intake

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Uncontrolled infection, Neurologic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with advanced osteosarcoma, a type of bone cancer that has recurred or spread. The treatment modifies a person's own immune cells (T cells) in a lab to enhance their ability to attack cancer cells. The trial evaluates the safety and optimal dose of these modified cells and assesses their effectiveness against the cancer. Suitable candidates have osteosarcoma that has worsened recently, despite other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all anti-cancer medications before joining the trial. There are specific waiting periods, like 7 days for chemotherapy and biologic agents, and 30 days for certain therapies, before you can start the trial.

Is there any evidence suggesting that FH-FOLR1 ST CAR T cells are likely to be safe for humans?

Research shows that FH-FOLR1 ST CAR T cells may help treat advanced osteosarcoma, a type of bone cancer. Although the safety in humans is still under investigation, early studies suggest these modified immune cells can effectively target and fight cancer cells.

The treatment involves altering a patient's immune cells to better attack cancer. Similar therapies have been well-tolerated. Patients receive chemotherapy drugs before this treatment to enhance its effectiveness. These drugs have known side effects, which are usually manageable.

Overall, early evidence from initial studies is promising. However, since this treatment is just beginning to be tested in humans, researchers are closely monitoring safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bone cancer, such as surgery, chemotherapy, and radiation, FH FOLR1 ST CAR T-cell therapy is unique because it uses genetically modified T-cells to specifically target cancer cells. Researchers are excited about this treatment because it harnesses the power of the immune system to recognize and attack cancer cells more precisely, potentially leading to fewer side effects compared to traditional therapies. This targeted approach could offer a more effective treatment option for patients who do not respond well to existing therapies.

What evidence suggests that this CAR T-cell therapy is effective for advanced osteosarcoma?

Research has shown that FH FOLR1 ST CAR T-cells, which participants in this trial will receive, could effectively treat advanced osteosarcoma, a type of bone cancer. In lab tests, these specially designed T-cells successfully attacked cancer cells with the FOLR1 protein. Studies with mice demonstrated that the treatment stopped tumors from growing and led to 100% survival over 190 days, with no tumors returning. These results suggest that FH FOLR1 ST CAR T-cells might be a strong option for fighting this aggressive cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Michelle Choe, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for patients with advanced osteosarcoma that has recurred or spread. Participants must have T cells that can be modified in the lab and should be able to undergo apheresis, imaging tests, chemotherapy, and other procedures required by the study.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

Life expectancy ≥ 8 weeks

Serum creatinine and bilirubin levels within specified limits

Exclusion Criteria

Concurrent use of other investigational anti-cancer agents

Uncontrolled concurrent illness

Significant underlying neurologic disease unless approved by PI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Lymphodepletion

Patients undergo leukapheresis for manufacturing of the FH-FOLR1 ST CAR T cell product and receive lymphodepleting therapy with fludarabine and cyclophosphamide

1 week

Multiple visits for leukapheresis and lymphodepletion

CAR T Cell Infusion

Patients receive FH-FOLR1 ST CAR T cells intravenously on day 0, 1, or 2

1 day

1 visit (in-person)

Initial Monitoring

Patients are monitored closely for at least 28 days after receiving CAR T cells, including blood sample collection and imaging studies

4 weeks

Frequent visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at specified intervals

Up to 10 years

Visits 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

What Are the Treatments Tested in This Trial?

Interventions

• FH FOLR1 ST CAR T-cells

Trial Overview The trial is testing FH-FOLR1 ST CAR T-cell therapy's safety and effectiveness against advanced osteosarcoma. Patients' own T cells are engineered to target tumor cells and are given back via infusion after pre-treatment with chemotherapy drugs like fludarabine and cyclophosphamide.

How Is the Trial Designed?

Group I: Treatment (FH-FOLR1 ST CAR T cells) Experimental Treatment 11 Interventions

Patients 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.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Washington Research Foundation

Collaborator

Trials

1

Recruited

100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12455178/

Preclinical Evaluation of Folate Receptor-α Chimeric ... FH FOLR1-CART exhibits robust in vitro activation and potent cytotoxicity against FOLR1-expressing osteosarcoma cell lines and primary ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07227571?rank=4

Genetically Engineered Cells (FH-FOLR1 ST CAR T ... FH-FOLR1 ST CAR T cells may be safe, tolerable, and/or effective in treating patients with advanced osteosarcoma. OUTLINE: This is a dose- ...

3. aacrjournals.org aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-25-0086/3648569/crc-25-0086.pdf

Preclinical evaluation of folate receptor-alpha chimeric ... cells in both groups by day 55. 342. FH FOLR1-CART exhibit anti-tumor activity against patient-derived osteosarcoma in vitro. 343.

4. asco.org asco.org/abstracts-presentations/ABSTRACT423258

Preclinical testing of FOLR1-CAR T cells against ... NT T treated mice with local disease demonstrated significant bone destruction; no local tumors were found in FOLR1-CAR T treated mice. HTC (CD45+/CD3+) ...

5. bioworld.com bioworld.com/articles/724278-folate-receptor-car-t-exhibits-preclinical-activity-in-osteosarcoma

Folate receptor α-CAR T exhibits preclinical activity in ... In osteosarcoma cell-line derived xenograft mice, treatment with FH FOLR1-CART (n=2) resulted in 100% overall survival at day 190 without signs ...

6. researchgate.net researchgate.net/publication/395357498_Preclinical_Evaluation_of_Folate_Receptor-a_Chimeric_Antigen_Receptor_T_Cells_Exhibits_Highly_Efficient_Antitumor_Activity_against_Osteosarcoma

(PDF) Preclinical Evaluation of Folate Receptor-α Chimeric ... These results demonstrate a potential therapeutic option for patients with advanced osteosarcoma. FH FOLR1-CART is advancing to an early-phase ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40919994/

Preclinical Evaluation of Folate Receptor-α Chimeric Antigen ... These results demonstrate a potential therapeutic option for patients with advanced osteosarcoma. FH FOLR1-CART is advancing to an early-phase ...