This is a phase I clinical study for patients with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, and the response to a combination of cyclophosphamide, autologous tumor-infiltrating lymphocytes (TILs), autologous dendritic cells (DCs), and OKT3 (anti-CD3 antibody), along with low-dose interleukin-2 (IL-2) therapy.
This is a phase I clinical study for patients with platinum-resistant (does not respond to platinum-based chemotherapy) high grade serous ovarian, fallopian tube, or primary peritoneal cancer. Prior to the main treatment, patients will receive cyclophosphamide by vein. Patients will then receive an infusion (given by vein) of autologous tumor-infiltrating lymphocytes (TILs) which will first be taken from the patient, then be stimulated with certain substances called autologous dendritic cells (DCs) and OKT3 (anti-CD3 antibody), and then given back to the patient as an infusion. This is believed to make the TILs work better. TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down. After infusion of TILs, low-dose interleukin-2 (IL-2) therapy will be given.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Intravenous infusions: Dose level 1 (3 patients): 3x10\^7 TILs (with maximum 3x10\^6 autologous dendritic cells); Dose level 2 (3 patients): 1x10\^8 TILs (with maximum 1x10\^7 autologous dendritic cells); Dose level 3 (3 patients): 3x10\^8 TILs (with maximum 3x10\^8 autologous dendritic cells)
Subcutaneous injections of IL-2 x 4 days during the first week and x 5 days the second week with 2 days of rest in between each week of dosing
Intravenous infusion: 30 mg/kg/day for 2 days (Day -3 and -2 prior to infusion of TILs)
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Number of occurrences and severity of side effects
Toxicities will be monitored on an ongoing basis by the investigators. Toxic effects will be categorized using the CTCAE v4.0 and will be reported using summary statistics. The highest toxicity for each patient in each category or subcategory will be described. Both events related and unrelated to treatment will be captured. The total number of episodes for each event reported, the severity and attribution to study therapy of each episode reported will also be displayed.
Time frame: Starting at first dose of study treatment up to 10 years
Clinical response to treatment
Evaluation of the clinical response (clinical tumor regression), which will be monitored and reported according to RECIST v1.1 criteria and Immune-Related Response Criteria.
Time frame: 6 weeks after treatment
Number of patients with an immunity and no immunity to the study treatment
Immunological assessments of peripheral blood mononuclear cells, serum and tissue biopsies (if any) will be reported using units appropriate to each particular assay. Results from immunohistochemical evaluations of tissue biopsies will be reported descriptively. Descriptive statistics will be used to summarize immunological findings. Any correlation with clinical response rate will be reported descriptively.
Time frame: From start of the study up to 11 years
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