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

Capital Medical University

Status and phase: Completed; Phase 1

Conditions: Hepatocellular Carcinoma

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03175679

Beijing Youan Ethics[2017]05

Details and patient eligibility

About

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).

Full description

PBMCs of enrolled patients were collected and then further separated by density gradient centrifugation. After washing three times, the cells were resuspended in serum-free medium with recombinant human IL-2 and α-GalCer. Restimulation with α-GalCer-pulsed autologous DCs was done on days 7. After 14 days of cultivation, the iNKT cells were harvested, washed thrice, and then resuspended in saline. The frequency of iNKT cells before and after cultured in vitro were determined by flow cytometry analysis.

Enrollment: 10 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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>3.5×10^9/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.

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 4 patient groups

iNKT cell loading dose:3x10^7/m2

Experimental group

Description:

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.

Treatment:

Drug: Tegafur

Drug: IL-2

Biological: iNKT cells

iNKT cell loading dose:6x10^7/m2

Experimental group

Description:

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.

Treatment:

Drug: Tegafur

Drug: IL-2

Biological: iNKT cells

iNKT cell loading dose:9x10^7/m2

Experimental group

Description:

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.

Treatment:

Drug: Tegafur

Drug: IL-2

Biological: iNKT cells

iNKT cell loading dose:1x10^10/m2

Experimental group

Description:

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.

Treatment:

Drug: Tegafur

Drug: IL-2

Biological: iNKT cells