Study of Adoptive Transfer of iNKT Cells Combined With TAE/TACE to Treat Unresectable HCC

NCT04011033 | Completed Phase 2 Results DMC

• 1 other identifier: Beijing Youan Ethics [2018]016
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. 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 their function is defective in liver cancer. After expansion and restored function in vitro, iNKT cells can home to liver, then they play key antitumor function. We have finished a phase I study of adoptive transfer of autologous iNKT cells for treating patients with unresectable HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study was to verify the effectiveness of iNKT cell infusion in patients with unresectable HCC who had previously failed transcatheter arterial embolization (TAE) / transcatheter arterial chemoembolization (TACE).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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. Progression is defined using Modified RECIST (mRECIST),as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

  From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.

Secondary Outcomes (5)

• Overall Survival(OS)

  From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.

• Objective Response Rate(ORR)

  Evaluation was performed at the 12th week after the start of the treatment.

• Disease Control Rate (DCR)

  Evaluation was performed at the 12th week after the start of the treatment.

• Adverse Events(AEs)

  The occurrence of AEs was observed for an average of 24 weeks after the completion of treatment (between 0-11 weeks of treatment) for up to a 60 week period in total.

• Time to Quality of Life (QoL) Deterioration

  Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks.

Study Arms (2)

TAE/TACE+iNKT for unresectable HCC

EXPERIMENTAL

TAE/TACE combined with autologous iNKT cells infusion will be applied for patients in experimental group. TAE/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, 9th, 11th week after first TAE/TACE therapy.

Biological: iNKT cells; Drug: Human recombinated Interleukin-2; Procedure: TAE/TACE

TAE/TACE for unresectable HCC

OTHER

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

Procedure: TAE/TACE

Interventions

iNKT cells BIOLOGICAL

5×10\^8-10\^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy.

Also known as: invariant Natural Killer T cells

TAE/TACE+iNKT for unresectable HCC

Human recombinated Interleukin-2 DRUG

IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion.

Also known as: IL-2

TAE/TACE+iNKT for unresectable HCC

TAE/TACE PROCEDURE

TAE/TACE will be conducted to all patients at 0th week and 4th week.

Also known as: Transcatheter Arterial embolization/Transcatheter Arterial chemoembolization

TAE/TACE for unresectable HCC; TAE/TACE+iNKT for unresectable HCC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years.
• Patients with hepatocellular carcinoma (BCLC, stageB/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 cell/mL in peripheral blood mononuclear cell (PBMC).
• Able to understand and sign the informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing YouAn Hospital: lead
• Beijing Shijitan Hospital, Capital Medical University: collaborator
• Beijing Ditan Hospital: collaborator

Study Sites (1)

Beijing Youan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

Related Publications (1)

• Guo J, Bao X, Liu F, Guo J, Wu Y, Xiong F, Lu J. Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial. J Hepatocell Carcinoma. 2023 Aug 21;10:1379-1388. doi: 10.2147/JHC.S416933. eCollection 2023.

  PMID: 37637501 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

One limitation of our study is that patients only received two cycles of TAE and the duration of iNKT therapy was only 3 months; thus, our study was not long enough to adequately assess OS. A second limitation was the small sample size, but our promising data prompts future studies in larger cohorts to more thoroughly delineate how iNKT cell therapy can be used in the context of TACE/TAE to improve therapeutic options for patients with unresectable HCC.

Results Point of Contact

• Title: Lu Jun
• Organization: BeijingYouan Hospital

lujun98@ccmu.edu.cn

+86-010-83997153

Study Officials

• Jun Lu, Director

  Beijing YouAn Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatology and Cancer Biotherapy Ward

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 8, 2019
• Study Start: March 1, 2018
• Primary Completion: March 1, 2020
• Study Completion: October 1, 2023
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)