Adoptive Transfer of iNKT Cells for Treating Patients With Relapsed/Advanced HCC

NCT03175679 | Completed Phase 1 Results DMC

• 1 other identifier: Beijing Youan Ethics[2017]05
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study enrolls patients who have relapsed/advanced hepatocellular carcinoma (HCC, BCLC stage C). The HCC tumor relapsed or metastasized through the body after standard treatment or the patients cannot receive standard treatment under current conditions. This research study uses special immune system cells called iNKT cells, a new experimental treatment. The purpose of this study is to find the biggest dose of iNKT cells that is safe and tolerance, to see how long they last in the body, to learn the immunoresponse in the body, to learn the side effects are and to see if the iNKT cells will help people with relapsed/advanced hepatocellular carcinoma (HCC).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  Defined as signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2.

  During the first 12 weeks, participants were assessed for adverse events every 2-4 weeks after infusion; after the first 12 weeks, participants were assessed for adverse events every 3 months, up to 20 months.

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Through study completion, an average of 12 months.

• Number of Participants With Stabilized (SD) or Progressive (PD) Disease.

  4 weeks, 8 weeks, 12 weeks and 24 weeks after cell infusion.

• Overall Survival (OS)

  Through study completion, up to 20 months.

Study Arms (4)

iNKT cell loading dose:3x10^7/m2

EXPERIMENTAL

Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC. iNKT Cell Loading Dose：3x10\^7/m2. IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days. Tegafur: Tegafur will be given at a dose of 40\~60 mg bis in die (BID) 2 weeks.

Biological: iNKT cells; Drug: IL-2; Drug: Tegafur

iNKT cell loading dose:6x10^7/m2

EXPERIMENTAL

Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC. iNKT Cell Loading Dose：6x10\^7/m2. IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days. Tegafur: Tegafur will be given at a dose of 40\~60 mg bis in die (BID) 2 weeks.

Biological: iNKT cells; Drug: IL-2; Drug: Tegafur

iNKT cell loading dose:9x10^7/m2

EXPERIMENTAL

Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC. iNKT Cell Loading Dose：9x10\^7/m2. IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days. Tegafur: Tegafur will be given at a dose of 40\~60 mg bis in die (BID) 2 weeks.

Biological: iNKT cells; Drug: IL-2; Drug: Tegafur

iNKT cell loading dose:1x10^10/m2

EXPERIMENTAL

Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC. iNKT Cell Loading Dose：1x10\^10/m2. IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days. Tegafur: Tegafur will be given at a dose of 40\~60 mg bis in die (BID) 2 weeks.

Biological: iNKT cells; Drug: IL-2; Drug: Tegafur

Interventions

iNKT cells BIOLOGICAL

The patients received different doses of in vitro-expanded autologous iNKT cells through intravenous infusion. The dosage was escalated from 3x10\^7 cells/m2 to 6x10\^7 cells/m2 to 9x10\^7 cells/m2. The maximum tolerated dose (MTD) was defined as the last dose level, and the dosage would be up to 1x10\^10 cells/m2 if no MTD was observed after a 3+3 design.

iNKT cell loading dose:1x10^10/m2; iNKT cell loading dose:3x10^7/m2; iNKT cell loading dose:6x10^7/m2; iNKT cell loading dose:9x10^7/m2

IL-2 DRUG

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

Also known as: Human recombinated Interleukin-2

iNKT cell loading dose:1x10^10/m2; iNKT cell loading dose:3x10^7/m2; iNKT cell loading dose:6x10^7/m2; iNKT cell loading dose:9x10^7/m2

Tegafur DRUG

Tegafur will be given at a dose of 40\~60 mg bis in die (BID) 2 weeks.

Also known as: Gimeracil and Oteracil Potassium Capsules

iNKT cell loading dose:1x10^10/m2; iNKT cell loading dose:3x10^7/m2; iNKT cell loading dose:6x10^7/m2; iNKT cell loading dose:9x10^7/m2

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, 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\>3.5×10\^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.

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

Study Sites (1)

Beijing Youan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Interleukin-2; Tegafur; gimeracil; potassium oxonate

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; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. LJUN
• Organization: BeijingYouanH

lujun98@ccmu.edu.cn

861366138148

Study Officials

• Jun Lu, Director

  Beijing YouAn Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatology and Cancer Biotherapy Ward

Model Details: Four planned loading dose of iNKT cells for 10 patients.

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: June 5, 2017
• Study Start: April 1, 2017
• Primary Completion: December 30, 2018
• Study Completion: March 30, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)