Clinical trial NCT03175679: Adoptive Transfer of iNKT Cells for Treating Patients With Relapsed/Advanced HCC
Official title: A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Lead sponsor: Beijing YouAn Hospital
Sponsor class: OTHER
First posted: 2017-06-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Four planned loading dose of iNKT cells for 10 patients.
Primary purpose: TREATMENT

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).

Detailed 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.

Eligibility 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\>3.5×10\^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.

Primary outcomes:
measure: Number of Adverse Events
timeFrame: 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:
measure: Progression-Free Survival (PFS)
timeFrame: Through study completion, an average of 12 months.
measure: Number of Participants With Stabilized (SD) or Progressive (PD) Disease.
timeFrame: 4 weeks, 8 weeks, 12 weeks and 24 weeks after cell infusion.
measure: Overall Survival (OS)
timeFrame: Through study completion, up to 20 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Youan Hospital,Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing YouAn Hospital
name: Jun Lu, Director
role: STUDY_CHAIR
References: