This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.
This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1ᶜ²⁵⁹T. The trial is conducted entirely with outpatient procedures; however, patients may be hospitalized for the cytoreductive chemotherapy at the discretion of the investigator. Upon enrollment, patients will undergo leukapheresis for T cell collection, and their cells will be genetically engineered and expanded ex vivo. Seven days prior to receiving T-cells patients will undergo a cyclophosphamide conditioning regimen to potentiate the immunotherapy. The cell product will be infused as a single infusion (Day 0, typically Monday) to mitigate risks associated with unanticipated infusion reactions. Patients will be followed daily for the first week, weekly until 4 weeks, 8 weeks, and 12 weeks and then at 6 months and every 3 months until disease progression. Patients will undergo disease monitoring by MRI/CT scan (as appropriate for disease) at baseline, day 28, 8 weeks and 12 weeks, and months 6, and every 3 months until progression. Tumor biopsies will be taken at baseline, Week 8, and upon progression. In patients who have progressive disease following initial infusion but whose tumors continue to express NY-ESO-1, these patients may be eligible for a second infusion with redirected T cells. At disease progression, the interventional portion of the protocol ends and long term follow-up (LTFU) begins, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Patients will receive at least 1x10⁹ transduced cells, however the target dose for this protocol is for patients to receive 5x10⁹ transduced cells with a maximum possible dose of 6x10⁹ administered as a single intravenous (IV) infusion.
City of Hope National Medical Center
Duarte, California, United States
Stanford Cancer Institute
Stanford, California, United States
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
MD Anderson Cancer Center
Houston, Texas, United States
Adverse Events Related to Study Treatment
Number of Participants with Adverse Events related to study treatment
Time frame: Up to 12 months
Tumor Response
Number of participants with response as assessed by Immune-related Response Criteria (irRC)
Time frame: Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression
Peak Persistence of Modified T-cells in the Peripheral Blood
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
Time frame: Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU
Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood.
Percentage of CD4+pentamer+ or CD8+pentamer+ cells expressing LAG-3, PD-1, TIM-3 in the functionality of NY-ESO-1ᶜ²⁵⁹T cells in the manufactured product and post-treatment blood.
Time frame: Weeks 4 and 8 post T-cell infusion
Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein
NY-ESO-1 expression as determined by Histoscore (H score). Histoscore (0-300) represents the amount of NY-ESO-1 protein present in the tissue sample. H-Score formula: \[1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)\] (It is not clearly established if NY-ESO-1 H score has an association with prognosis.)
Time frame: Screening and at Baseline
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