Engineered Immune Effectors Against Ovarian Cancer

Study Overview
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Brief Summary
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This is a single-arm, open-label, phase I/II trial to evaluate the safety and efficacy of ovarian cancer specific cytotoxic lymphocytes (OC-CTLs) in women.

Detailed Description
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Ovarian cancer is a cancer that forms in or on an ovary. The majority of ovarian cancers arise from the epithelium (outer lining) of the ovary. In 2015 it was reported found in 1.2 million women and resulted in 161,100 deaths worldwide. Among women it is the seventh-most common cancer and the eighth-most common cause of death from cancer. Treatment for ovarian cancer consists of surgery, chemotherapy, immunotherapy and sometimes, radiotherapy. The kind of treatment depends on many factors, including the type of ovarian cancer, its stage and grade, as well as the general health of the patient. Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of ovarian cancer specific cytotoxic T lymphocytes in patients.

Official Title
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Intervention of Ovarian Cancer Based on Engineered Immune Effectors (EIEs)

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Biological: OC-CTLs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, informed consent obtained prior to any study-specific procedures. Age older than 10 years. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1. Expected survival ≥ 12 weeks. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage II-IV. Not pregnant, and on appropriate birth control if of childbearing potential. Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1,000/mm^3; platelet (PLT) ≥ 100,000/mm^3. Proper renal and hepatic functions (ULN denotes upper limit of normal range) with serum creatinine ≤ 2×ULN; serum bilirubin ≤ 2×ULN; AST/ALT ≤ 2×ULN; ALKP ≤ 5×ULN; serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome. Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test were negative. Exclusion Criteria: Patients with ovarian tumors with low malignant potential (i.e. borderline tumors); Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment). Previous treatment of adoptive T cell therapy. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations). Pregnant or lactating females. Inadequate bone marrow function with absolute neutrophil count < 1,000/mm^3; platelet count < 100,000/mm^3; Hb < 9 g/dL. Inadequate liver and renal function with serum (total) bilirubin > 1.5 x ULN; AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases); alkaline phosphatase > 2.5 x ULN; serum creatinine >2.0 mg/dl (> 177 μmol/L); urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr. Serious active infection requiring i.v. antibiotics at during screening. Subject infected with HCV (HCV antibody positive), HBV (HBsAg positive), and HIV (HIV antibody positive),Treponema pallidum antibody positive or TB culture positive.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OC-CTLs<br>Autologous ovarian cancer specific cytotoxic lymphocytes | Biological: OC-CTLs<br>* 2 to 4 infusions, once a week, for 1x10^5 4x10^6 CTLs/kg via IV, abdominal cavity or tumor injection each time<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OC-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events | Physiological parameter (measuring cytokine response, fever, symptoms) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional analyses of OC-CTLs in vitro | The specificity of OC-CTLs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT). | 4 weeks | 
| Anti-tumor effects | Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OC-CTL, Ovarian cancer, Cytotoxic lymphocyte