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

November 11, 2019 updated by: Beijing 302 Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100039
        • Recruiting
        • The Fifth Medical Center of PLA General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Targeted drug combined with allogeneic NK cell treatment group
In addition to traditional symptomatic supportive treatment, Sorafenib, regolfinib or levabinib will be administered in combination with allogeneic NK cells (3 cycles).
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.
No Intervention: Targeted drug treatment group
Sorafenib, regolfinib or levabinib will be administered in addition to traditional symptomatic supportive care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: From the date of enrollment to the end of two years of follow-up.
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.
Overall survival
Time Frame: From the date of enrollment to the end of two years of follow-up.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate
Time Frame: From the date of enrollment to the end of two years of follow-up.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing 302 Hospital

Collaborators

Shenzhen Third People's Hospital
The first People's Hospital of Zhengzhou

Investigators

  • Study Chair: Fusheng Wang, Beijing 302 Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

August 6, 2019

First Submitted That Met QC Criteria

November 11, 2019

First Posted (Actual)

November 14, 2019

Study Record Updates

Last Update Posted (Actual)

November 14, 2019

Last Update Submitted That Met QC Criteria

November 11, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • beijing302-NK-HCC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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