CT Antigen TCR-redirected T Cells for Ovarian Cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/IIa, Open Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Patients With Recurrent or Treatment Refractory Ovarian Cancer.|
- NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: At apheresis: Day -30 (±10 days) until month 9, LTFU (Years 1-15) ] [ Designated as safety issue: Yes ]To determine the safety and tolerability of autologous redirected T cell therapy in patients with treatment refractory or resistant Stage III/IV ovarian cancer.
- Tumor Response [ Time Frame: Baseline, Day 28, 8 weeks and at Months 3, 6, and 9, LTFU (Years 1-15) ] [ Designated as safety issue: No ]Evaluate correlates of treatment efficacy by measuring 1) Clinical response rates to treatment based on irRC and progression free survival, 2) to evaluate the persistence of genetically modified cells in the peripheral blood, and as possible at tumor sites, and 3) to evaluate the phenotype and functionality of genetically modified cells isolated from peripheral blood and, as possible, from tumor sites post infusion.
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||January 2019|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
This is an open label clinical trial. Patients with the HLA-A201 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1c259 T cells.
Biological: NY-ESO-1c259 T cells
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. A total dose of 0.5-1e10 total cells will be administered on consecutive days as a split dose of 30% (Day 0) and 70% (Day 1) by intravenous (IV) infusion.
This is an open label clinical trial. Patients with the HLA-A201 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1c259 T. 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 split infusion (30% Day 0 and 70% Day 1; typically Monday and Tuesday) 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 9 months. 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 9 or until progression, whichever comes first. Optional tumor biopsies will be taken at baseline, at Day 28, and upon progression, if applicable.
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 9 months, the interventional portion of the protocol ends and long term follow‐up (LTFU) begins at 1 year, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01567891
|Contact: RPCI Hotlinefirstname.lastname@example.org|
|United States, California|
|City of Hope National Medical Center||Recruiting|
|Durate, California, United States, 91010|
|Contact: Mihaela Cristea, MD 626-256-4673 ext 63155 email@example.com|
|Principal Investigator: Mihaela Cristea, MD|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Kunle Odunsi, MD, PhD 716-845-3497 Kunle.Odunsi@roswellpark.org|
|Principal Investigator: Kunle Odunsi, MD, PhD|
|Study Chair:||Kunle Odunsi, MD, PhD||Roswell Park Cancer Institute|