Administration of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) and Containing the Inducible Caspase 9 Safety Switch in Subjects With Recurrent Platinum Resistant Epithelial Ovarian Cancer
UNC Lineberger Comprehensive Cancer Center
Summary
The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) in patients with ovarian cancer that came back after receiving standard therapy for this cancer. The iC9.CAR.B7-H3 treatment is experimental and has not been approved by the Food and Drug Administration. The study team wants to know how much (dose) of the iC9-CAR.B7-H3 T cells are safe to use in patients without causing too many side effects and what is the maximum dose could be tolerated. There are two parts to this study. In part 1, approximately blood will be collected from subjects to prepare the iC9.CAR.B7-H3 T cells. The study team will collect disease-fighting T cells from the blood and modify them to prepare the iC9.CAR.B7-H3 T cells. In part 2, the iC9.CAR.B7-H3 T cells will be given to eligible subjects by infusion three days after completion of lymphodepletion chemotherapy.
Description
This phase 1, single-center, open-label study to determine the safety of escalating dosing of chimeric antigen receptor T (CAR-T) cells targeting the B7-H3 antigen and containing the inducible caspase 9 safety switch (iC9-CAR.B7-H3 T cells) administered to adult subjects with relapsed or refractory platinum-resistant epithelial ovarian cancer. The safety of iC9-CAR.B7-H3 T cells administered intraperitoneally via a port/catheter will be investigated using a modified 3+3 design with a starting dose of 1 ×106. The data from the dose escalation will be used to determine a recommended phase 2 dose…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: 1. Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study: 2. Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject. 3. Age ≥ 18 years at the time of consent. 4. Eastern Cooperative Oncology Group (ECOG) of 0-2. 5. The subject must have histologically or cytologically confirmed epithelial ovarian, peritoneal or fallopian tube cancer and must have a histological diagnosis…
Interventions
- BiologicaliC9-CAR.B7-H3 T cells
iC9-CAR.B7-H3 T cells will then be administered intraperitoneally
- DrugCyclophosphamide
cyclophosphamide 300 mg/m2 IV will be given.
- DrugFludarabine
fludarabine 30 mg/m2 IV will be given.
Location
- Lineberger Comprehensive Cancer CenterChapel Hill, North Carolina