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

Phase

Condition

Osteosarcoma

Sarcoma

Treatment

UB_TT170

SCRI-E2CAR_EGFRtv1

Clinical Study ID

NCT05312411

ENLIGHTen-01

Ages 15-30
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Refractory or recurrent/progressive osteosarcoma that has failed first line therapyfor Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and isnot amenable to surgical resection (must meet one of the following):

New site of measurable disease by radiographic imaging or histologicconfirmation
New site of evaluable disease by radiographic imaging (including FDG-PET) orhistologic confirmation
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 existinglesion(s) (previously irradiated lesions may be included)
Persistent measurable disease or FDG-PET avid bone metastasis that has failedto achieve complete remission to upfront conventional therapy (surgery,radiotherapy and/or chemotherapy)

Able to tolerate apheresis, including placement of temporary apheresis catheter, ifnecessary, 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-tumorantibody therapy, genetically modified cell therapy, and, if no apheresis productavailable, corticosteroid therapy (excluding physiologic replacement), discontinuedwithin 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 effectivecontraception through 12 months following final stud drug infusion

Exclusion

Exclusion Criteria:

Active malignancy other than primary malignant solid tumor diagnosis (CNSintracranial 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 yearfollow up
Presence of any condition that, in the opinion of the investigator, would prohibitthe subject from undergoing treatment under this protocol.

Study Design