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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04011033
Recruitment Status : Recruiting
First Posted : July 8, 2019
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
LU JUN, Beijing YouAn Hospital

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: iNKT cells Drug: Cyclophosphamide Drug: Human recombinated Interleukin-2 Procedure: TACE Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

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 Name: 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 Name: 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 Name: IL-2

Procedure: TACE
TACE will be conducted to all patients at 0th week and 4th week.
Other Name: Transcatheter Arterial Chemoembolization

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 Name: Transcatheter Arterial Chemoembolization




Primary Outcome Measures :
  1. 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.

  2. 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. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04011033


Contacts
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Contact: Jun Lu, Director 86-13661381489 lujun98@ccmu.edu.cn
Contact: Jia Guo, Clinician 86-18612238992 15210775497@163.com

Locations
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China, Beijing
Beijing Youan Hospital,Capital Medical University Recruiting
Beijing, Beijing, China, 100069
Contact: Xuli Bao, Clinician    86-13161935299    bxli2001@163.com   
Sponsors and Collaborators
Beijing YouAn Hospital
Investigators
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Study Chair: Jun Lu, Director Beijing YouAn Hospital
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Responsible Party: LU JUN, Director of Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital
ClinicalTrials.gov Identifier: NCT04011033    
Other Study ID Numbers: Beijing Youan Ethics[2019]034
First Posted: July 8, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Cyclophosphamide
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents