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Study of Adoptive Transfer of iNKT Cells Combined With TACE to Treat Advanced HCC

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
iNKT cells
Cyclophosphamide
Human recombinated Interleukin-2
TACE
Sponsored by
Beijing YouAn Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-80 years.
  • Patients with hepatocellular carcinoma (BCLC, stage C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time.
  • Life expectancy of ≥ 12 weeks.
  • WBC>3.0×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.
  • iNKT>10/mL in peripheral blood mononuclear cell (PBMC).
  • Able to understand and sign the informed consent.

Exclusion Criteria:

  • Any uncontrolled systematic disease: hypertension, heart disease, and et al.;
  • Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;
  • Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;
  • Unstable immune systematic diseases or infectious diseases;
  • Combined with AIDS or syphilis;
  • Patients with history of stem cell or organ transplantation;
  • Patients with allergic history to related drugs and immunotherapy;
  • Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage;
  • Pregnant or lactating subjects;
  • Unsuitable subjects considered by clinicians.

Sites / Locations

  • Beijing Youan Hospital,Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

TACE+iNKT for unresectable HCC

TACE for unresectable HCC

Arm Description

TACE combined with autologous iNKT cells infusion will be applied for patients in experimental group. TACE will be performed at 0th and 4th week. 5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 8th and 12th week.

TACE will be conducted at 0th week and 4th week.

Outcomes

Primary Outcome Measures

Overall Survival(OS)
OS is the duration from the date of enrollment to the date of death due to any causes.
Progression-Free Survival(PFS)
PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression.
Disease Control Rate (DCR)
DCR is the proportion of patients who had a response rate including complete remission (CR), partial remission (PR) and disease stabilization (SD) evaluated by imaging according to the irRC standard.

Secondary Outcome Measures

Immunological Monitoring
Frequencies of immune cells such as iNKT cells, natural killer cells (NK) , regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), et al will be analyzed by flow cytometry before and after iNKT infusion.
Adverse Events(AEs)
The severities of AEs will be divided into 5 levels according to the National Cancer Institute (NCI) Common Terminology Standard for Adverse Events (CTCAE) version 4.03.
Alpha-fetoprotein (AFP)
AFP is the best-defined tumor marker for HCC, and it is widely used in clinical settings as an adjuvant diagnostic and prognostic indicator.

Full Information

First Posted
July 3, 2019
Last Updated
July 5, 2019
Sponsor
Beijing YouAn Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04011033
Brief Title
Study of Adoptive Transfer of iNKT Cells Combined With TACE to Treat Advanced HCC
Official Title
Study of Adoptive Transfer of Invariant Natural Killer T Cells Combined With Transcatheter Arterial Chemoembolization (TACE) to Treat Advanced Hepatocellular Carcinoma (HCC): Phase II Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing YouAn Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients are first diagnosed with late-stage and unresectable, their effective drugs and treatments are very limited. invariant Natural Killer T (iNKT) cell exhibit antitumor activity against malignant tumors through producing high levels of cytokines. iNKT cells are abundant in the liver, but defect in liver cancer development. iNKT cells can express homing receptors licensing them specifically to migrate liver, then play key antitumor immunity. We already did a phase I study of autologous infusion of iNKT cells in the treatment of patients with advanced HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study is to verify the effectiveness of iNKT cells infusion combined with transcatheter arterial chemoembolization (TACE) in treatment of advanced HCC.
Detailed Description
Patients with advanced HCC will be enrolled and divided into two groups. Patients in experimental group will be treated with TACE combined with iNKT cells infusion. TACE will be performed at 0th and 4th week. iNKT cells will be infused at 1st, 3rd, 5th, 7th, 8th and 12th week. Patients in control group will be treated with TACE at 0th and 4th week. Adverse events（AEs）, overall survival (OS) time and recurrence-free survival (RFS) time, change of immune cells will be monitored.

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 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TACE+iNKT for unresectable HCC
Arm Type
Experimental
Arm Description
TACE combined with autologous iNKT cells infusion will be applied for patients in experimental group. TACE will be performed at 0th and 4th week. 5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 8th and 12th week.
Arm Title
TACE for unresectable HCC
Arm Type
Other
Arm Description
TACE will be conducted at 0th week and 4th week.
Intervention Type
Biological
Intervention Name(s)
iNKT cells
Other Intervention Name(s)
invariant Natural Killer T cells
Intervention Description
5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 8th and 12th week.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
CTX
Intervention Description
CTX will be administered intravenously at a dose of 750mg/m2 2 days before the first iNKT cells infusion.
Intervention Type
Drug
Intervention Name(s)
Human recombinated Interleukin-2
Other Intervention Name(s)
IL-2
Intervention Description
IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion.
Intervention Type
Procedure
Intervention Name(s)
TACE
Other Intervention Name(s)
Transcatheter Arterial Chemoembolization
Intervention Description
TACE will be conducted to all patients at 0th week and 4th week.
Primary Outcome Measure Information:
Title
Overall Survival(OS)
Description
OS is the duration from the date of enrollment to the date of death due to any causes.
Time Frame
3 months or up to death
Title
Progression-Free Survival(PFS)
Description
PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression.
Time Frame
3 months or up to death
Title
Disease Control Rate (DCR)
Description
DCR is the proportion of patients who had a response rate including complete remission (CR), partial remission (PR) and disease stabilization (SD) evaluated by imaging according to the irRC standard.
Time Frame
3 months or up to death
Secondary Outcome Measure Information:
Title
Immunological Monitoring
Description
Frequencies of immune cells such as iNKT cells, natural killer cells (NK) , regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), et al will be analyzed by flow cytometry before and after iNKT infusion.
Time Frame
Frequencies of immune cells will be monitored at 0th, 4th, 8th and 12th week.
Title
Adverse Events(AEs)
Description
The severities of AEs will be divided into 5 levels according to the National Cancer Institute (NCI) Common Terminology Standard for Adverse Events (CTCAE) version 4.03.
Time Frame
The occurrence and severities of AEs will be recorded within 12-13 weeks after iNKT cells infusion.
Title
Alpha-fetoprotein (AFP)
Description
AFP is the best-defined tumor marker for HCC, and it is widely used in clinical settings as an adjuvant diagnostic and prognostic indicator.
Time Frame
3 months or up to death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-80 years. Patients with hepatocellular carcinoma (BCLC, stage C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time. Life expectancy of ≥ 12 weeks. WBC>3.0×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value. iNKT>10/mL in peripheral blood mononuclear cell (PBMC). Able to understand and sign the informed consent. Exclusion Criteria: Any uncontrolled systematic disease: hypertension, heart disease, and et al.; Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors; Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment; Unstable immune systematic diseases or infectious diseases; Combined with AIDS or syphilis; Patients with history of stem cell or organ transplantation; Patients with allergic history to related drugs and immunotherapy; Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage; Pregnant or lactating subjects; Unsuitable subjects considered by clinicians.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Lu, Director
Phone
86-13661381489
Email
lujun98@ccmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Jia Guo, Clinician
Phone
86-18612238992
Email
15210775497@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Lu, Director
Organizational Affiliation
Beijing YouAn Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing Youan Hospital,Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100069
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xuli Bao, Clinician
Phone
86-13161935299
Email
bxli2001@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Adoptive Transfer of iNKT Cells Combined With TACE to Treat Advanced HCC

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