Safety Evaluation of Autologous Dendritic Cell Anticancer Immune Cell Therapy (Cellgram-DC)

Study Overview
=================
Brief Summary
-----------------
This Phase 1 study to evaluate the safety of cancer immunotherapy with autologous dendritic cells in patients with advanced or recurrent epithelial ovarian cancer

Detailed Description
-----------------
To evaluate the safety of an autologous dendritic cell(DC) anticancer immune cell therapy (Cellgram-DC) for the treatment of advanced or recurrent epithelial ovarian cancer.

Official Title
-----------------
An Open Label, Single-center, Phase 1 Study to Evaluate the Safety of Cancer Immunotherapy With Autologous Dendritic Cells in Patients With Advanced or Recurrent Epithelial Ovarian Cancer

Conditions
-----------------
Ovarian Cancer

Intervention / Treatment
-----------------
* Biological: Cellgram-DC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 19 and under 80 years Patients with Fédération Internationale de Gynécologie et d' Obstétrique(FIGO) stage III with histologically confirmed advanced or recurrent epithelial ovarian cancer (Serous, endometrioid, and mucinous only), fallopian tube cancer, and primary peritoneal cancer (residual tumor size <1cm) Patients who have undergone tumor reduction or staging and complete or plan to complete platinum-based chemotherapy In case of complete or partial response in primary or secondary chemotherapy Whole body performance status: European Cooperative Oncology Group(ECOG) 0 1 Patients whose BRCA gene mutation test results can be confirmed Patients whose life expectancy is at least 6 months or longer Hb ≥ 8.0 g/dL, Absolute Neutrophil Count(ANC) ≥ 1,500/mm3, Platelets ≥ 100,000/mm3 Serum Creatinine ≤ 1.5 x Upper Limit of Normal(ULN) or Serum Creatinine> 1.5 x ULN and Calculated Creatinine Clearance> 30 mL/min Total Bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN, Aminotransferase (AST)/Alanine aminotransferase(ALT) <2.5 x ULN Patients who did not receive surgery, radiation therapy, or immunotherapy within the last 6 weeks and recovered from side effects Patients who agreed to use a medically recognized contraceptive method (diaphragm method used with spermicide, abstinence) during participation in the clinical trial (injection or implantable hormone therapy is not appropriate). Patients who voluntarily participated in clinical trials and signed the Informed Contents Form (ICF) Exclusion Criteria: Patients with malignant tumors other than non-melanoma skin cancer in the past 3 years Patients with brain metastases Patients who previously received anti-tumor immunotherapy (anti-PD1, anti-PDL1 or anti-PDL2, etc.) or participated in immunotherapy-related clinical trials Patients with active autoimmune diseases requiring systemic immunosuppression treatment (e.g., immunosuppressants such as cyclosporin A or azathioprine, or steroids for disease control) Patients who use or plan to use Poly (ADP-ribose) polymerase (PARP) inhibitors due to the confirmed Breast Cancer Susceptibility Gene(BRCA) 1 or BRCA 2 mutation Patients with medical conditions requiring continuous or intermittent administration of systemic steroids or immunosuppressants Patients who received blood products (limited to whole blood products) within 4 weeks of screening criteria, or patients who received colony stimulating factors (Colony Stimulating Factor or recombinant Erythropoietin) Patients with a history of organ or hematopoietic stem cell transplantation Patients with acute or chronic infections requiring systemic treatment Patients known to be infected with human immunodeficiency virus (HIV)/serum positive Patients with active hepatitis A, B or C Patients with untreated syphilis Patients expected to need systemic chemotherapy, biotherapy, or immunotherapy for therapeutic purposes Patients who received live virus vaccines (e.g. measles, mumps, rubella, chickenpox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), oral typhoid vaccine, Flu-Mist, etc.) within 30 days Patients with a history of anaphylaxis to gentamicin Pregnant or breastfeeding patients Others, if the person in charge of the study determines that it is not suitable for the clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cellgram-DC<br>Cellgram-DC is injected Subcutaneous injection near the upper arm lymph nodes | Biological: Cellgram-DC<br>* Patients will receive 3 times every 2 weeks injection of Cellgram-DC(Autologous dendritic cell) subcutaneous injection near the upper arm lymph nodes<br>* Other names: Autologous dendritic cell anticancer immune cell therapy for the treatment of ovarian cancer in patients with advanced or recurrent epithelial ovarian cancer;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Measure CTCAE of Safety | The level of Adverse Event (AE) is described in accordance with the Common Terminology Criteria for Adverse Event (CTCAE) (Version 5.0). | -5, -3, 0, 2, 4, 8, 16 and 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response evaluation (INF-r) | The tumor antigen-specific immune response induced after administration compared to before Investigational Product(IP) administration was confirmed by measuring changes in the secretion of cytokines (INF-r) in serum (ELISA). | 0, 2, 8, 16 and 28 weeks | 
| Immune response evaluation (IL-12) | The tumor antigen-specific immune response induced after administration compared to before Investigational Product(IP) administration was confirmed by measuring changes in the secretion of cytokines (IL-12) in serum (ELISA). | 0, 2, 8, 16 and 28 weeks | 
| Measurement of changes in tumor marker test results (CA-125) | Changes in tumor marker test results (CA-125) are measured at each time point (V4, V5, V6, V7, V8) after administration compared to before (V3) Investigational Product(IP) administration. | 0, 2, 4, 8, 16 and 28 weeks | 
| Evaluation of solid tumor reflection at the time of follow-up observation | Responses of target/non-target lesions evaluated by the solid tumor reflection evaluation criteria (RECIST 1.1) at the time of follow-up (V6, V8) | 8 and 28 weeks |