Safety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

Safety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04162158
• Other study ID #: beijing302-NK-HCC
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2019
• Est. completion date: October 1, 2024

Study information

• Verified date: April 2019
• Source: Beijing 302 Hospital
• Contact: Junliang Fu
• Phone: 010-66-933332
• Email: fjunliang[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label, paired control study to evaluate the safety and clinical efficacy of allogeneic NK cells combined with targeted drug in the treatment for advanced HCC.

Description:

Since killer cell immunoglobulin-like receptor (KIR) mismatch can inhibit the negative regulatory signal of autologous major histocompatibility complex (MHC) molecules and ensure sufficient NK cell activation, allogeneic NK cells therapy, as a potential therapeutic option for tumor, has achieved good results in patients with acute myeloid leukemia. In this study, investigators evaluate the safety and efficacy of allogeneic NK cells in the treatment of advanced HCC. 200 patients from three hospitals will be enrolled in this study and followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donor and cultured in vitro for 15 days and infused to the patient in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, impact indicators, hematology, biochemical indicators, and immunological indicators to evaluate the safety and efficacy of the treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• According to the 2010 edition of the diagnostic criteria for primary liver cancer BCLC, the patient was diagnosed as advanced hepatocellular carcinoma by pathology and imaging (BCLC C phase);

• Child-Pugh A/B (5-9), Eastern Cooperative Oncology Group (ECOG) PS score less than 2 points;

• Laboratory criteria:

1. Liver function: Child A/B, ALT < 200 U/L, AST < 200 U/L, Tbil <51µmol/L

2. Renal function: Creatinine clearance = 60ml/minute

3. Hematologic function: PLT =40×10`9/L, WBC =2×10`9/L, HGB>80 g/L

4. Cardiac function: No abnormality in cardiac enzyme and ECG

• Survival expectation is greater than 6 months;

• Patients with active hepatitis B or C were treated with the appropriate NA or DAA medication, and all patients enrolled in the group were treated with targeted drugs.

• The patient has a donor who meets the donor enrollment criteria and all patients and donors sign the Informed Consent Form;

Exclusion Criteria:

• Women who are pregnant or breast-feeding.

• Co-infected with hepatitis A, hepatitis E, AIDS or other infectious diseases.

• Patients with serious complications such as acute infection and gastrointestinal bleeding within 30 days.

• Patients with other serious systemic and psychiatric diseases.

• Exposure to any cell therapy such as, but not limited to CIK, DC, CTL , PD-1 and stem cells therapy 6 months prior to study drug administration.

• Other conditions that researchers believe may increase the risk of subjects or lead to affected study results, such as the presence of mental illness in subjects.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• allogeneic NK cells therapy
PBMC was isolated from the peripheral blood of the donors and infused to the patient after 14 days incubation. In each cycle, patients will be infused 4.0-5.0×10`9 allogeneic NK cells. All patients in the experimental group received a total of three cycles of treatment with one month interval between each treatment.

Locations

Country	Name	City	State
China	The Fifth Medical Center of PLA General Hospital	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Beijing 302 Hospital	Shenzhen Third People's Hospital, The first People's Hospital of Zhengzhou

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events	Incidence of Treatment-Emergent Adverse Events as assessed by [National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0]	From the date of enrollment to the end of two years of follow-up.
Primary	Overall survival	Overall Survival (OS) defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for at least five years.	From the date of enrollment to the end of two years of follow-up.
Secondary	Disease control rate	According to the RECIST criteria, patients with complete response (CR), partial response (PR), and stable disease (SD) were imaged.	From the date of enrollment to the end of two years of follow-up.