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

• ClinicalTrials.gov Identifier: NCT03662477
• Recruitment Status: Unknown
• First Posted: September 7, 2018
• Last Update Posted: December 6, 2019
• Sponsor: Shenzhen Fifth People's Hospital
• Information provided by (Responsible Party): LiuTao, Shenzhen Fifth People's Hospital

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
NK Cell Mediated Immunity	Biological: NK cells	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effect of Autologous NK Cell Immunotherapy on Advanced Lung Adenocarcinoma With EGFR Mutation: a Preliminary Clinical Study
• Actual Study Start Date: January 1, 2018
• Estimated Primary Completion Date: December 20, 2019
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

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 Name: 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 Name: randomized
No Intervention: EGFR-NK-; The EGFR mutation negative patients were with the principles of randomized and without NK cells treatment.

Outcome Measures

Primary Outcome Measures :

1. Clinical response [ Time Frame: Calculated the sum area of all tumors 3 months after NK treatment ]
   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).

Secondary Outcome Measures :

1. Detection of immune function [ Time Frame: Before and 3 months after NK cell therapy ]
   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.
2. Analysis of tumor biomarker CEA and CA125 levels in serum [ Time Frame: Before and 3 months after NK cell therapy ]

   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.

Other Outcome Measures:

1. The endpoints of interest were progression-free survival (PFS). [ Time Frame: The KPS scores were collected pre-treatment and at 12 months post-treatment. ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. -

Contacts and Locations

Contacts

Contact: TAO LIU, PHD; 13682481027; 13682481027@163.com

Locations

China, Guangdong

Shenzhen Luohu Hospital; Recruiting

Shenzhen, Guangdong, China, 518000

Contact: TAO LIU, PHD 13682481027 13682481027@163.com

Contact: Meiling Zhou, Master 13068724206 754793494@qq.com

Sponsors and Collaborators

Shenzhen Fifth People's Hospital

More Information

• Responsible Party: LiuTao, Principal Investigator, Shenzhen Fifth People's Hospital
• ClinicalTrials.gov Identifier: NCT03662477
• Other Study ID Numbers: Shenzhen Fifth Hospita
• First Posted: September 7, 2018
• Last Update Posted: December 6, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Adenocarcinoma of Lung; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site