FITC-E2 CAR T Cells + Folate-Fluorescein for Osteosarcoma

Overseen By Catherine Albert, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Anticancer agents

Disqualifiers: Active malignancy, Severe infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for osteosarcoma, a type of bone cancer, particularly in cases unresponsive to existing treatments or recurring after treatment. Researchers are testing a combination of genetically modified immune cells, called CAR T cells (specifically, FITC-E2 CAR T Cells), and a new drug, UB-TT170, to determine if they can jointly target and destroy cancer cells. Participants may qualify if they have osteosarcoma that hasn’t improved with previous treatments and are willing to undergo a process to modify their immune cells. The active treatment period lasts about 8 months, with follow-ups extending up to 15 years. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial requires that certain medications, like anti-cancer agents, radiotherapy, chemotherapy, and some others, be stopped within a specific 'washout' period (time without taking certain medications) before participating. It's best to discuss your current medications with the trial team to see if they need to be paused.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatment under study, which includes special immune cells called SCRI-E2CAR_EGFRtv1 CAR T cells and a drug called UB-TT170, contains important safety information. In trials, patients with osteosarcoma received set amounts of these CAR T cells, followed by increasing amounts of UB-TT170. Some patients experienced changes in cytokine levels, which indicate how well the immune system functions.

These trials test safety and feasibility, checking if the treatment can be administered without major issues. The study remains in the early stages, focusing mainly on safety. Researchers are looking for side effects and are still collecting data. It's important to know that these treatments are experimental and not yet proven safe or effective for everyone.

For those considering joining the trial, it's helpful to understand that this is an early-stage study, concentrating on determining the treatment's safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment using FITC-E2 CAR T Cells combined with Folate-Fluorescein for osteosarcoma because it offers a new, targeted approach. Unlike traditional chemotherapy or surgery, which can have widespread effects on the body, this treatment uses CAR T cells, a type of immune cell engineered to specifically recognize and attack cancer cells. The addition of folate-fluorescein helps enhance the targeting process, potentially leading to more effective eradication of the tumor while minimizing damage to healthy tissues. This precision targeting could offer new hope for patients with osteosarcoma, a challenging cancer to treat with current options.

What evidence suggests that this trial's treatments could be effective for osteosarcoma?

Research has shown that CAR T cells can effectively destroy osteosarcoma cancer cells, suggesting they might be a promising targeted treatment for this type of cancer. In this trial, participants will receive CAR T cells followed by UB-TT170. This combination tags the cancer cells, making it easier for the modified T cells to attack them. Although osteosarcoma is difficult to treat, this method offers a new way to combat the cancer. Early studies have been encouraging, but researchers are still testing its effectiveness in people. More research is needed to confirm its effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Catherine Albert, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for patients with osteosarcoma that's resistant to treatment or has returned. Participants must have a new site of disease confirmed by imaging, be able to undergo apheresis, and have a life expectancy of at least 8 weeks. They should not have HIV or hepatitis, agree to use contraception if applicable, and have good organ function. Exclusions include active severe infections, other cancers, primary immunodeficiency syndrome, pregnancy/breastfeeding, and any condition preventing protocol adherence.

Inclusion Criteria

Negative HIV, hepatitis B and C test within 3 months

I can undergo apheresis or already have an apheresis product ready for use.

My osteosarcoma has not responded to the first treatment and cannot be removed with surgery.

Exclusion Criteria

I have no active cancer other than my primary solid tumor.

Pregnant or breast feeding

Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and CAR T Cell Manufacturing

Blood is drawn from participants to extract T cells, which are then modified in a lab to become CAR T cells.

4-6 weeks

Treatment

Participants receive chemotherapy followed by CAR T cell infusion and escalating doses of UB-TT170.

8 months

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants who received CAR T cell infusion are monitored for long-term safety and outcomes.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• SCRI-E2CAR_EGFRtv1
• UB_TT170

Trial Overview

The study tests UB-TT170 combined with modified CAR T cells against osteosarcoma. Patients' T cells are collected and engineered in the lab to target cancer flagged by UB-TT170. After chemotherapy preparation, these CAR T cells are infused back into the patient followed by regular doses of UB-TT170 to mark cancer cells for destruction by CAR T cells.

How Is the Trial Designed?

Group I: UB-TT170 following SCRI-E2CAR_EGFrtv1 Experimental Treatment 2 Interventions

Following CAR T cell administration, subjects will receive a first Course of 3 escalating doses of UB-TT170 over 2 weeks followed by fixed weekly dosing for 2 weeks. If eligible, subjects may proceed to Courses 2 - 4 consisting of 7 weekly doses of UB-TT170.

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Umoja Biopharma

Industry Sponsor

Trials

1

Recruited

110+

Umoja BioPharma, Inc.

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

GD2 CAR modified T cells were found to be highly effective in killing osteosarcoma (OS) tumor cells, indicating their potential as a targeted immunotherapy for high-risk OS in children.

The study also revealed that combining GD2 CAR T cells with suboptimal doses of doxorubicin chemotherapy can enhance the cytotoxic effects against OS, suggesting a synergistic approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas. Chulanetra, M., Morchang, A., Sayour, E., et al.[2020]

CAR-T cell therapy has shown high remission rates in pediatric patients with CD19+ B-cell malignancies, but challenges remain for treating solid tumors like osteosarcoma due to fewer targets and a hostile tumor environment.

The development of a CAR-T adaptor molecule (EC17 CAM) allows for targeted therapy against folate receptor-positive tumors, enhancing CAR-T cell activation and reducing the risk of severe cytokine release syndrome through careful dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies. Lu, YJ., Chu, H., Wheeler, LW., et al.[2020]

The engineered FR806 receptor allows for the selective targeting and elimination of T cells that have been modified for therapy, minimizing damage to normal tissues, which is crucial for safety in adoptive T cell therapies.

In experiments with immuno-compromised mice, the antibody-drug conjugate CH12-MMAF effectively eliminated most of the FR806-expressing T cells, demonstrating the efficacy of this safety switch in controlling T cell populations post-therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells. Wu, X., Shi, B., Zhang, J., et al.[2018]

Citations

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The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes ...

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FITC-E2 CAR T Cells + Folate-Fluorescein for Osteosarcoma

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The study examines the safety and feasibility of administering a fixed dose of autologous peripheral blood-derived CD4 and CD8 T cells that have ...

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A trial demonstrated significant cytokine level changes and CAR T-cell expansion in patients with osteosarcoma, with some experiencing dose- ...