A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

Osteosarcoma Clinical Trial

Official title:

A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-Ew) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05312411
• Other study ID #: ENLIGHTen-01
• Status: Recruiting
• Phase: Phase 1
• Start date: May 20, 2022
• Est. completion date: April 30, 2040

Study information

• Verified date: June 2023
• Source: Seattle Children's Hospital
• Contact: Catherine Albert, MD
• Phone: 206-987-2106
• Email: immunotherapy[@]seattlechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy.

In this study, researchers will take some of your blood and remove the T cells in a process called "apheresis". Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body.

A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells.

The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: April 30, 2040
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 30 Years

Eligibility

Inclusion Criteria:

• Refractory or recurrent/progressive osteosarcoma that has failed first line therapy for Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following):

1. New site of measurable disease by radiographic imaging or histologic confirmation

2. New site of evaluable disease by radiographic imaging (including FDG-PET) or histologic confirmation

3. Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a maximum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included)

4. Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy)

• Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing

• Life expectancy = 8 weeks

• Lansky or Karnofsky score = 50

• Anti-cancer agents, radiotherapy, cytoxic chemotherapy, biologic therapy, anti-tumor antibody therapy, genetically modified cell therapy, and, if no apheresis product available, corticosteroid therapy (excluding physiologic replacement), discontinued within protocol specified wash-out period

• Adequate hematologic, renal, hepatic, cardiac, and respiratory function.

• Negative HIV, hepatitis B and C test within 3 months

• If of child-bearing or fathering potential, willing to use highly effective contraception through 12 months following final stud drug infusion

Exclusion Criteria:

• Active malignancy other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed)

• Ongoing, symptomatic CNS pathology requiring medical intervention

• Receiving external beam radiotherapy

• Presence of active, severe infection

• Primary immunodeficiency syndrome

• Pregnant or breast feeding

• Unwilling to provide consent/assent for study participation, including 15 year follow up

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

Related Conditions & MeSH terms

• Osteosarcoma
• Sarcoma

Intervention

Biological:
• SCRI-E2CAR_EGFRtv1
Autologous CD4+ and CD8+ T cells that have been genetically modified to express antiFL(FITC-E2)

Drug:
• UB_TT170
Bispecific small molecule adapter formulated with phosphate buffered saline

Locations

Country	Name	City	State
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Children's Hospital	Umoja BioPharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events associated with ex-vivo expanded autologous T cells genetically modified to express an antiFL(FITC-E2) CAR administered with UB-TT170 will be assessed	The type, frequency, severity, and duration of adverse events will be summarized	30 days
Secondary	Ability to manufacture antiFL(FITC-E2) CAR cells	The number of successfully manufactured antiFL(FITC-E2) CAR products will be assessed	28 Days
Secondary	Evaluate the pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells	Pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells	25 days