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

July 5, 2019 updated by: LU JUN, Beijing YouAn Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

144

Phase

  • Phase 2
  • Phase 3

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, 100069
        • Recruiting
        • Beijing Youan Hospital,Capital Medical University
        • Contact:

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 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TACE+iNKT for unresectable HCC
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.
Biological: iNKT cells
5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 8th and 12th week.
Other Names:
  • invariant Natural Killer T cells
Drug: Cyclophosphamide
CTX will be administered intravenously at a dose of 750mg/m2 2 days before the first iNKT cells infusion.
Other Names:
  • CTX
Drug: Human recombinated Interleukin-2
IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion.
Other Names:
  • IL-2
Procedure: TACE
TACE will be conducted to all patients at 0th week and 4th week.
Other Names:
  • Transcatheter Arterial Chemoembolization
Other: TACE for unresectable HCC
TACE will be conducted at 0th week and 4th week.
Procedure: TACE
TACE will be conducted to all patients at 0th week and 4th week.
Other Names:
  • Transcatheter Arterial Chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival(OS)
Time Frame: 3 months or up to death
OS is the duration from the date of enrollment to the date of death due to any causes.
3 months or up to death
Progression-Free Survival(PFS)
Time Frame: 3 months or up to death
PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression.
3 months or up to death
Disease Control Rate (DCR)
Time Frame: 3 months or up to death
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.
3 months or up to death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunological Monitoring
Time Frame: Frequencies of immune cells will be monitored at 0th, 4th, 8th and 12th week.
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.
Frequencies of immune cells will be monitored at 0th, 4th, 8th and 12th week.
Adverse Events(AEs)
Time Frame: The occurrence and severities of AEs will be recorded within 12-13 weeks after iNKT cells infusion.
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.
The occurrence and severities of AEs will be recorded within 12-13 weeks after iNKT cells infusion.
Alpha-fetoprotein (AFP)
Time Frame: 3 months or up to death
AFP is the best-defined tumor marker for HCC, and it is widely used in clinical settings as an adjuvant diagnostic and prognostic indicator.
3 months or up to death

Collaborators and Investigators

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

Sponsor

Beijing YouAn Hospital

Investigators

  • Study Chair: Jun Lu, Director, Beijing YouAn 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)

December 31, 2020

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

July 3, 2019

First Submitted That Met QC Criteria

July 5, 2019

First Posted (Actual)

July 8, 2019

Study Record Updates

Last Update Posted (Actual)

July 8, 2019

Last Update Submitted That Met QC Criteria

July 5, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Beijing Youan Ethics[2019]034

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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