Clinical Study on Anti-tumor Effect Induced by Activated Primary Natural Killer（NK）Cells

This study will analyze and evaluate the following items:

1. The safety of natural killer（NK） cells for treatment of subjects with solid tumors. Forty patients will be enrolled for each of the five cancers (in total 200 patients will be enrolled).
2. The effectiveness of natural killer（NK）cell therapy alone or with chemotherapy or targeted drugs.

Subjects from 18 to 75 years of age who are diagnosed with a solid tumor including pancreatic cancer, lung cancer, breast cancer, ovarian cancer and colon cancer, and for whom standard treatments are not effective, may be eligible for this study. Participants undergo the following procedures:

Peripheral blood will be collected from a vein of arm. Peripheral blood mononuclear cells（PBMC） will be isolated and purified for NK manufacturing. After 14~21 days cultivation, activated NK will be harvested and formulated for clinical administration.

Subjects will receive NK cell treatment by intravenous infusion. The frequency is once every 3 or 4 weeks for the first 3 months. Participants who respond well after 3 months may be eligible to continue NK cell therapy; and those not may receive NK therapy combined with chemotherapy and/or targeted drugs, or chemotherapy/targeted drugs alone.

Evaluations during therapy including:

1. Clinical assessment, and history of medications;
2. Blood draws for routine and research tests, including but not limited to: lymphocyte population and circulating tumor cell analysis in peripheral blood;
3. CT scan, bone scan and positron emission tomography（PET ）scan, if indicated, for disease evaluation;
4. Pharmacokinetics study after NK infusion. For this test, the number of NK cells in the blood is measured over time at indicated time-points.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Pancreatic Cancer; Ovarian Cancer; Lung Cancer; Colon Cancer
• Intervention / Treatment: Biological: Activated NK

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital
      • Contact: Zhiguo Chen
      • Sub-Investigator: Yu Zhao, PhD
      • Sub-Investigator: Fei Li, MD
      • Sub-Investigator: Hua Kang, MD
      • Sub-Investigator: Shijun Wang, MD
      • Sub-Investigator: Yi Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 18 to 75 years (including boundary values);
2. Diagnosed with histologically and cellularly confirmed cancer of lung, breast, pancreas, ovary, or colon;
3. At least 8 weeks since any prior systemic therapy to treat the underlying malignancy (standard or investigational);
4. Life expectancy > 6 months, and performance status（KPS）> 60 points;

5. Organ functions meet the following criteria:

   1. Blood bilirubin < 2mg/dL,
   2. Aspartate transaminase（AST）<100 IU/L,
   3. Alanine transaminase（ALT） <100 IU/L,
   4. Creatinine <1.5 mg/dL,
   5. Urea nitrogen ≤ 25 mg/dL,
   6. Hemoglobin ≥ 9.0 g/dL,
   7. White blood cell count>3.5×109/L,
   8. Neutrophil count >1.5x109/L,
   9. Platelet count > 80 × 109 /L,
   10. Hematocrit >0.20,
6. No severe infections.

Exclusion Criteria:

1. Subjects who take combined systemic steroids within 2 weeks prior to treatment (except inhaled steroids);
2. Patients who take chemotherapy within 1 month prior to treatment;
3. Subjects receiving drugs that stimulate the production of bone marrow hematopoietic cells within two weeks prior to treatment;
4. Patients with T lymphoma and NK cell lymphoma;
5. Patients with autoimmune diseases, including but not limited to lupus erythematosus, rheumatoid arthritis, etc.;
6. Seriously uncontrollable infected patients;
7. Patients who are allergic to the biological agents in this treatment;
8. Patients with organ transplantation or organ failure;
9. Subjects with severe cardiovascular disease and severe renal failure;
10. Patients who are undergoing treatment of immunosuppressive drugs or long-term administration of immunosuppressive drugs after organ transplantation;
11. Patients with active infection or fever;
12. Subjects with severe cardiovascular and cerebrovascular diseases, diabetes and renal dysfunction;
13. Subjects with pregnancy or during the lactating period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NK cells; Activated NK from peripheral blood and/or umbilical cord blood（UCB）	Biological: Activated NK; Cell suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of toxicity induced by NK infusion	The incidence of toxicity within each infusion within 6 months after NK administration	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective-response rate (ORR)	Objective-response rate (ORR): defined as the proportion of patients who achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time on study.	6 months after 6 infusions of NK administration
Persistence of NK	Duration of NK persistence: defined as duration from Day 1 to the time when the NK level goes back to stable level	Day 0, Day 7, Day30, Day 60, Day 90, Day 180

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Study Director: Zhiguo Chen, PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 26, 2018
• Primary Completion (ANTICIPATED): September 30, 2021
• Study Completion (ANTICIPATED): September 30, 2022

Study Registration Dates

• First Submitted: August 3, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (ACTUAL): August 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: XuanWuH-NK

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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