Back to resultsSafety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
allogeneic NK cells therapy
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
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:
- Liver function: Child A/B, ALT < 200 U/L, AST < 200 U/L, Tbil <51μmol/L
- Renal function: Creatinine clearance ≥ 60ml/minute
- Hematologic function: PLT ≥40×10'9/L, WBC ≥2×10'9/L, HGB>80 g/L
- 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.
Sites / Locations
- The Fifth Medical Center of PLA General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Targeted drug combined with allogeneic NK cell treatment group
Targeted drug treatment group
Arm Description
In addition to traditional symptomatic supportive treatment, Sorafenib, regolfinib or levabinib will be administered in combination with allogeneic NK cells (3 cycles).
Sorafenib, regolfinib or levabinib will be administered in addition to traditional symptomatic supportive care.
Outcomes
Primary Outcome Measures
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]
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.
Secondary Outcome Measures
Disease control rate
According to the RECIST criteria, patients with complete response (CR), partial response (PR), and stable disease (SD) were imaged.
Full Information
NCT ID
NCT04162158
First Posted
August 6, 2019
Last Updated
November 11, 2019
Sponsor
Beijing 302 Hospital
Collaborators
Shenzhen Third People's Hospital, The first People's Hospital of Zhengzhou
1. Study Identification
Unique Protocol Identification Number
NCT04162158
Brief Title
Safety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma
Official Title
Safety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
October 1, 2022 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing 302 Hospital
Collaborators
Shenzhen Third People's Hospital, The first People's Hospital of Zhengzhou
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Targeted drug combined with allogeneic NK cell treatment group
Arm Type
Experimental
Arm Description
In addition to traditional symptomatic supportive treatment, Sorafenib, regolfinib or levabinib will be administered in combination with allogeneic NK cells (3 cycles).
Arm Title
Targeted drug treatment group
Arm Type
No Intervention
Arm Description
Sorafenib, regolfinib or levabinib will be administered in addition to traditional symptomatic supportive care.
Intervention Type
Biological
Intervention Name(s)
allogeneic NK cells therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
Incidence of Treatment-Emergent Adverse Events as assessed by [National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0]
Time Frame
From the date of enrollment to the end of two years of follow-up.
Title
Overall survival
Description
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.
Time Frame
From the date of enrollment to the end of two years of follow-up.
Secondary Outcome Measure Information:
Title
Disease control rate
Description
According to the RECIST criteria, patients with complete response (CR), partial response (PR), and stable disease (SD) were imaged.
Time Frame
From the date of enrollment to the end of two years of follow-up.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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:
Liver function: Child A/B, ALT < 200 U/L, AST < 200 U/L, Tbil <51μmol/L
Renal function: Creatinine clearance ≥ 60ml/minute
Hematologic function: PLT ≥40×10'9/L, WBC ≥2×10'9/L, HGB>80 g/L
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Junliang Fu
Phone
010-66-933332
Email
fjunliang@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yunbo Xie
Phone
010-66-933331
Email
15110140963@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fusheng Wang
Organizational Affiliation
Beijing 302 Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
The Fifth Medical Center of PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100039
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fu-Sheng Wang, MD
Phone
01066933328
Email
fswang302@163.com
First Name & Middle Initial & Last Name & Degree
Fu-Sheng Wang, MD
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Allogeneic NK Cells Therapy in Patients With Advanced Hepatocellular Carcinoma
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