NK Cells Infusion for Advanced Malignancies

A Clinical Research of Natural Killer (NK) Cells Infusion for the Treatment of Advanced Malignant Tumor

This study is designed to explore the safety and efficacy of natural killer (NK) cell infusion as treatment for patients with advanced malignant tumors after multiline therapy, and to evaluate the pharmacokinetics of NK cells in patients

Study Overview

• Status: Unknown
• Conditions: Immunotherapy
• Intervention / Treatment: Biological: NK cells infusion

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • Anhui Provincial cancer center
      • Contact: Yue-Yin Pan, PhD; Phone Number: 0086-551-62283411; Email: yueyinpan1965@163.com
      • Contact: Wei Wang, MD; Phone Number: 0086-551-62283411; Email: whouwei@gmail.com
      • Principal Investigator: Yue-Yin Pan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with advanced malignant tumors diagnosed by pathological histology and/or cytology who have failed multi-line therapy and have no standard treatment method are unable to undergo surgery, radiation therapy, or chemotherapy;
2. Age 18-75 years old (≥18, ≤75);
3. ECOG: 0-1;
4. Priority should be given to the inclusion of ovarian cancer, malignant leukemia, lymphoma, etc. that have been shown to respond well to NK cell therapy;
5. Expected survival period ≥ 3 months;
6. Hematology tests also meet the following requirements:

1) WBC≥3×109/L, ANC≥1.5×109/L, Hb≥90g/L, PLT≥100×109/L; 2) TBIL ≤ 1.5 × ULN (normal upper limit), ALT and AST ≤ 2 × ULN (if there is liver metastasis, then ≤ 5 × ULN); 3) Endogenous creatinine clearance ≥ 60 ml/min (calculated based on Cockcroft-Gault formula); (7) Length of solid tumors do not exceed 6 cm; (8) Signing of informed consent from each patient

Exclusion Criteria:

1. History of other malignancies with a disease-free period <5 years (except for cured basal cell carcinoma of the skin, cured carcinoma of the cervix in situ, and gastrointestinal tumors proven to be cured by endoscopic mucosal resection);
2. Patients with brain metastases (unless the investigator believes that brain metastasis is currently stable, it is generally not recommended for enrollment);
3. Transplant recipients;
4. T-cell lymphoma patients;
5. Allergies to biologics used in this treatment;
6. Patients with HIV and syphilis;
7. HBV carriers;
8. Patients who are undergoing radiation therapy or immunotherapy within 4 weeks;
9. Patients who have undergone high-dose radiation therapy on the lung and liver within 4 months;
10. Patients with pulmonary inflammation determined by chest radiography;
11. Oxygen saturation ≤ 90% on room air;
12. Patients with cachexia caused by advanced tumors;
13. Long-term use of immunosuppressive drugs or patients who are using immunosuppressive drugs;
14. Those with serious autoimmune diseases;
15. Patients with organ failure (grade 4 of heart function; liver function with Child class C or above; brain metastasis with disturbance of consciousness; severe respiratory failure symptoms);
16. Active infections (including intra-abdominal infections).
17. Researchers consider it inappropriate to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NK cells infusion

Biological: NK cells infusion; Pretreatment：patients enrolled in this study will receive 20 mg/kg of cyclophosphamide for solid tumor or 20-60 mg/kg of cyclophosphamide for hematological tumor once daily for 3 times. NK cells infusion is allowed within 2-14 days after treatment. NK cells infusion：30-60 minutes before infusion，ant-allergic agents are applied (promethazine 25mg,i.m. ; Cimetidine 0.4g i.v. ; diphenhydramine 50mg po.). NK cells are intravenously infused into patients with 15-30 minutes every other day for one to three times. The number of every infused NK cells is 1-3×10^7/kg, counted as the number of CD56+ cells. Patients with severe pleural or ascites can also receive pleural or abdominal cavity perfusion simultaneously. The total number of infused NK cells is no more than 5×10^9 cells. 4 hours after NK cells infusion，IL-2 is applied every other day for six times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful expansion of NK cells in patient's circulatory system	CD56 positive cells ≥100 cells/μL in blood is considered as successful expansion of NK cells	7 days after the last treatment
Objective Response Rate	The percentage of patients who reach complete response（CR）or partial response （PR）after all treatment finished. The response is evaluated according to irRECIST.	4 weeks after all the treatment finished

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The interval time from the date when patients are enrolled into study to death or the last visit	1 and 2 years after treatment
Disease progression free survival	The interval time from the date when patients are enrolled into study to disease progression, death or last visit	1 and 2 years after treatment
Dynamic changes of NK cells number in blood	Numbers of CD56 positive cell in peripheral blood	Day 1,3,5,7,10,14,21,28 and 2, 3, 6 months after NK cells infusion finished

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Yueyin Pan, PhD, Anhui Province Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: NK cell infusion
• Other Study ID Numbers: AHP2018070101

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