Effect of NK Cell Immunotherapy on Advanced Lung Adenocarcinoma Adenocarcinoma With EGFR Mutation

Effect of Autologous NK Cell Immunotherapy on Advanced Lung Adenocarcinoma With EGFR Mutation: a Preliminary Clinical Study

This study was attempted to investigate the efficiency of NK cells immunotherapy on non-small cell lung cancer with and without EGFR mutation, and evaluated response rate (RR) and the progression-free survival (PFS).

Study Overview

• Status: Unknown
• Conditions: NK Cell Mediated Immunity
• Intervention / Treatment: Biological: NK cells

Detailed Description

Investigators will enrolle 100 patients who met the enrollment criteria. 50 patients were clinically confirmed EGFR mutation positive. They were divided into two groups (group A and group C according to if accepted NK therapy) in accordance with the principles of randomized. The rest 50 patients which were EGFR mutation negative were also divided into two groups (group B and group D) in accordance with the principles of randomized to be paired respectively with group A and group C. Comparison of lymphocyte number, serum tumor related biomarkers, circulating Tumor Cell (CTC), KPS and survival curves was carried out before after NK cell immunotherapy. The safety and short-term effects were evaluated followed by the median PDA, response rate assessment.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Luohu Hospital
      • Contact: TAO LIU, PHD; Phone Number: 13682481027; Email: 13682481027@163.com
      • Contact: Meiling Zhou, Master; Phone Number: 13068724206; Email: 754793494@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The criteriaof the enrollment are as following: (1) expected survival>6 months; (2) age between35-75 years old; (3) KPS >45; (4) platelets>80 × 109/L, WBC>3 × 109/L, hemoglobin>90g/L, prothrombin time-international normalized ratio (0.8-1.5), adequate hepatic function (bilirubin < 20 μM, aminotransferase<60 U/L) and renal function (serum creatinine < 130 μM, serum urea <10 mM); (5) All patients confirmed by pathology and/or imaging;

Exclusion Criteria:

The absence of level 3 hypertension, severe coronary disease, myelosuppression, respiratory disease, acute or chronic infection, and autoimmune diseases. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGFR+NK+; The EGFR mutation positive patients were with the principles of randomized and NK cells treatment.	Biological: NK cells; NK cells were generated in good manufacturing practice (GMP) condition. In brief, PBMCs were isolated from 50mL patient's blood with Ficoll-Hypaque(Morecell Biomedical Co. Ltd., Shenzhen, China). Then the Human NK Cell Culture Kit (Cat. No. MCF-004, Morecell Biomedical Co. Ltd., Shenzhen, China) and Serum-free Medium for NK Cells (MCM-002, Morecell Biomedical Co. Ltd., Shenzhen, China) was used for induction of NK cells according to the manufacturer's instructions. Three days before NK cell transfusion, the NK cells were sampled and sent to detect the NK cell quality.; Other Names: randomized
No Intervention: EGFR+NK-; The EGFR mutation positive patients were with the principles of randomized and without NK cells treatment .
Experimental: EGFR-NK+; The EGFR mutation negative patients were with the principles of randomized and NK cells treatment .	Biological: NK cells; NK cells were generated in good manufacturing practice (GMP) condition. In brief, PBMCs were isolated from 50mL patient's blood with Ficoll-Hypaque(Morecell Biomedical Co. Ltd., Shenzhen, China). Then the Human NK Cell Culture Kit (Cat. No. MCF-004, Morecell Biomedical Co. Ltd., Shenzhen, China) and Serum-free Medium for NK Cells (MCM-002, Morecell Biomedical Co. Ltd., Shenzhen, China) was used for induction of NK cells according to the manufacturer's instructions. Three days before NK cell transfusion, the NK cells were sampled and sent to detect the NK cell quality.; Other Names: randomized
No Intervention: EGFR-NK-; The EGFR mutation negative patients were with the principles of randomized and without NK cells treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Based on the Response Evaluation Criteria Solid Tumors (RECIST), the therapeutic effect was divided into complete response (CR), partial response (PR),stable disease (SD), progressive disease (PD). Investigators calculated the sum area of all tumors 3 months after NK treatment. The recent curative effect must have been maintainedat >4 weeks; CR + PR denoted the effective response rate (RR).	Calculated the sum area of all tumors 3 months after NK treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of immune function	Patients were detected Lymphocyte subgroups of 1ml peripheral blood by Flow cytometer (BD FACSCalibur), which inclunde the T cell number, CD4T cell number, CD8 T cell number and NK cell number.	Before and 3 months after NK cell therapy
Analysis of tumor biomarker CEA and CA125 levels in serum	Patients were detected the Serum Carcinoembryonic antigen (CEA) and CA125 level by Elisa kit.Investigators compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation. factor to identify patients tumor recurrence.We then compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation.	Before and 3 months after NK cell therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The endpoints of interest were progression-free survival (PFS).	Investigators evaluated the Karnofsky Performance Status (KPS) according to the comprehensive assessment of clinical activity, disease level, and self-care ability. Status (KPS) according to the comprehensive assessment of clinical activity, disease level, and self-care ability.	The KPS scores were collected pre-treatment and at 12 months post-treatment.

Collaborators and Investigators

• Sponsor: Shenzhen Fifth People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): December 20, 2019
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: August 19, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung
• Other Study ID Numbers: Shenzhen Fifth Hospita

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No