Hepatocellular CarcinomaPhase 1NCT03175679
Adoptive Transfer of iNKT Cells for Treating Patients With Relapsed/Advanced HCC
A Phase 1 study testing iNKT cells, IL-2 and Tegafur in people with Hepatocellular Carcinoma, run by Beijing YouAn Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- iNKT cells, IL-2 and Tegafur
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2017to 30 Mar 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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 locations and contacts
1 site in 1 country.
China1 site
Beijing Youan Hospital,Capital Medical University
Beijing, Beijing Municipality, 100069
About this study
Official title: A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)
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).
Read the 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- iNKT cells, IL-2, Tegafur
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iNKT cellsBiological
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.
IL-2Drug
Also called Human recombinated Interleukin-2
IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
TegafurDrug
Also called Gimeracil and Oteracil Potassium Capsules
Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: iNKT cells; Drug: IL-2; Drug: Tegafur |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
PFS is the time that passes from the date that patient enrolled in the clinical trial and the date on which HCC progresses or the date on which the patient dies. HCC progression was evaluated by imaging according to the irRC standard. Progression is defined as a ≥25% increase in the nadir of the sum of target lesions.
Measured: Through study completion, an average of 12 months.
Number of Participants With Stabilized (SD) or Progressive (PD) Disease.
Disease stabilization (SD) or progressive diseasee (PD) were valuated by imaging according to the irRC standard. Complete response (CR): Disappearance of all lesions; Partial response (PR): ≥50% decrease from baseline; SD: Neither CR or PD is met; PD≥25% increase in the nadir of the sum of target lesions.
Measured: 4 weeks, 8 weeks, 12 weeks and 24 weeks after cell infusion.
Overall Survival (OS)
OS is the time that passes from the date that patient enrolled in the clinical trial and the date on which the patient dies, according to the irRC standard.
Measured: Through study completion, up to 20 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start1 Apr 2017
- Primary completion30 Dec 2018
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Four planned loading dose of iNKT cells for 10 patients.
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing YouAn Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LU JUN, Beijing YouAn Hospital
- Investigators
- Jun Lu, Director, Study chair, Beijing YouAn Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03175679
- Sponsor's protocol ID
- Beijing Youan Ethics[2017]05
- Status last verified
- Sep 2024
- First submitted
- 24 May 2017
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT03175679
- Acronym / sponsor ID
- Beijing Youan Ethics[2017]05
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Beijing YouAn HospitalUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 5 Jun 2017 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Four planned loading dose of iNKT cells for 10 patients.
| Arm | Type | Receives |
|---|---|---|
| iNKT cell loading dose:3x10^7/m2 | Experimental | Biological: iNKT cells, Drug: IL-2, Drug: TegafurAutologous 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. |
| iNKT cell loading dose:6x10^7/m2 | Experimental | Biological: iNKT cells, Drug: IL-2, Drug: TegafurAutologous 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. |
| iNKT cell loading dose:9x10^7/m2 | Experimental | Biological: iNKT cells, Drug: IL-2, Drug: TegafurAutologous 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. |
| iNKT cell loading dose:1x10^10/m2 | Experimental | Biological: iNKT cells, Drug: IL-2, Drug: TegafurAutologous 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iNKT cellsThe 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. | Biological | 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-2Also: Human recombinated Interleukin-2IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days. | Drug | 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 |
| TegafurAlso: Gimeracil and Oteracil Potassium CapsulesTegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks. | Drug | 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 |
Primary outcome
Number of Adverse Events
Time frame: 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.
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.
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Through study completion, an average of 12 months.
Number of Participants With Stabilized (SD) or Progressive (PD) Disease.
Time frame: 4 weeks, 8 weeks, 12 weeks and 24 weeks after cell infusion.
Overall Survival (OS)
Time frame: Through study completion, up to 20 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jun Lu, Director study chair
Beijing YouAn Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing iNKT cells, IL-2 and Tegafur in people with Hepatocellular Carcinoma, run by Beijing YouAn Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.