Safety and feasibility of autologous cytokine induced killer (CIK) cells infusion as an adjuvant therapy in post resection hepatocellular carcinoma (HCC) patients
The primary objective of the study is to evaluate the safety of CIK cell infusion. Secondary objectives include assessment of feasibility, Recurrence‑Free Survival, Overall Survival, and Cancer‑Specific Survival.
Design
The study is designed as a prospective clinical trial involving CIK cell infusion.
Settings and conduct
The study will be conducted at the Liver Transplant Center of Imam Khomeini Hospital.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
1- Age between 18 and 80 years.
2- Patients with documented hepatocellular carcinoma at BCLC stage 0–A who have undergone surgical tumor resection.
3- Confirmation of cancer‑free status one month after surgery.
4- Provision of written informed consent.
5- Laboratory eligibility criteria including:
Leukocyte count > 3 × 10⁹ cells/L.
Absolute neutrophil count (ANC) ≥ 1000 cells/µL.
Hemoglobin ≥ 8.5 g/dL.
Platelet count > 50 × 10⁹/L.
Blood urea nitrogen (BUN) and serum creatinine ≤ 1.5 × upper limit of normal.
Exclusion Criteria:
1-Presence of active infection or uncontrolled viremia
2- Receipt of any cell therapy or immunotherapy within the past six months, or participation in another clinical study.
3- Presence of another malignancy (previous or concurrent) with a different primary site or histological characteristics from HCC.
4- History of clinically significant cardiovascular disease
5- History of organ transplantation.
6- Primary or secondary immunodeficiency, or presence of active autoimmune disease.
7- Severe allergic disorders or history of anaphylactic reactions.
8- Pregnancy or breastfeeding at the time of study entry.
9- Women who intend to become pregnant.
Intervention groups
Eligible patients will receive adjuvant autologous CIK cells following tumor resection.
Main outcome variables
The primary outcome is the evaluation of the safety of autologous CIK cell infusion.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20201229049871N1
Registration date:2026-05-30, 1405/03/09
Registration timing:prospective
Last update:2026-05-30, 1405/03/09
Update count:0
Registration date
2026-05-30, 1405/03/09
Registrant information
Name
massoud vosough
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2356 2000
Email address
masvos@royaninstitute.org
Recruitment status
recruiting
Funding source
Expected recruitment start date
2026-07-23, 1405/05/01
Expected recruitment end date
2028-07-22, 1407/05/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Safety and feasibility of autologous cytokine induced killer (CIK) cells infusion as an adjuvant therapy in post resection hepatocellular carcinoma (HCC) patients
Public title
Safety and feasibility of autologous cytokine-induced killer (CIK) cell injection as adjuvant therapy in hepatocellular carcinoma
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age between 18-80
Patients with Documented HCC in BCLC stage 0-A who have undergone surgical resection of the tumor. • Single or ≤ 3 nodules ≤ 3cm. • Liver function level according to Child Pugh Score A-B. • Patient performance level according to ECOG criteria 0-1
Establishment of Cancer free state one month after surgery
Obtaining of Informed Consent
Leukocyte count is bigger than (3 billion cells/L)
Absolute Neutrophil Count (ANC) is bigger than or equal to 1,000/µL
Hemoglobin is bigger than or equal to 8.5 g/dL
Thrombocyte count is bigger than (50 billion cells/L)
BUN and serum Creatinine is less than or equal to 1.5 multiply normal upper-limit
Exclusion criteria:
Receiving any cellular or immunotherapy treatment in the past six months or participation in another study
Concomitant (previous or concurrent) that differs from HCC in primary site or histological features.
History of clinically significant cardiovascular disease (such as heart failure, serious arrhythmias, or symptomatic coronary artery disease)
History of organ trnasplant
Primary or secondary immunodeficiency, or active autoimmune diseases
Having a severe allergic disorder or a history of anaphylactic reaction
Presence of active infection or uncontrolled viremia (especially HBV, HCV, or HIV)
Pregnancy or breastfeeding at the time of study entry
Women of childbearing age who are planning to become pregnant
Age
From 18 years old to 80 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
6
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Royan Research Institute
Street address
3th Floor, Block A, Ministry of Health and Medical Education Headquarters, Simaye Iran Street, between South Falamak and Zarafshan, Shahrak‑e Gharb
City
Tehran
Province
Tehran
Postal code
4364 - 14155
Approval date
2026-02-17, 1404/11/28
Ethics committee reference number
IR.ACECR.ROYAN.REC.1404.049
Health conditions studied
1
Description of health condition studied
Hepatocellular Carcinoma
ICD-10 code
C22.0
ICD-10 code description
Liver cell carcinoma
Primary outcomes
1
Description
Safety: Safety is defined as the frequency, type, severity, and suspected relatedness of adverse events associated with intravenous infusion of autologous CIK cells. All adverse events (AEs) and serious adverse events (SAEs) will be recorded from the time of the first infusion until the end of the follow-up period and will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Timepoint
Safety assessment and determination of possible adverse events (systemic, local, short-term, and serious) after intravenous injection of autologous cytokine-induced killer cells (CIK) will be performed at weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and at months 3 and 6 after injection.
Method of measurement
Safety assessment and determination of possible adverse events will be performed by taking history and examination according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.
Secondary outcomes
1
Description
Recurrence-Free Survival (RFS): Defined as the time interval from the date of study enrollment to the occurrence of the first tumor recurrence (intrahepatic or extrahepatic) or death from any cause, whichever occurs first.
Timepoint
Recurrence‑Free Survival (RFS) will be assessed during a 6‑month follow‑up period according to the study schedule, which includes regular clinical evaluations and imaging every 3 months. Time to recurrence or death will be measured from the date of study enrollment.
Method of measurement
Recurrence will be determined based on standard imaging findings (MRI and CT scan) and clinical assessment, and the date of the event will be recorded.
2
Description
Overall Survival (OS): Defined as the time interval from the date of study enrollment to the date of death from any cause.
Timepoint
Overall survival will be assessed at study enrollment and subsequently during regular follow‑up according to the study schedule until the end of the follow‑up period. Survival status will be recorded at each visit (weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and months 3 and 6 after infusion).
Method of measurement
Survival status will be documented through clinical follow‑up, review of medical records, and telephone contact if necessary.
3
Description
Cancer‑Free Survival (CFS): Defined as the time interval from the date of study enrollment to the first occurrence of cancer recurrence (intrahepatic or extrahepatic) or death from any cause, whichever occurs first.
Timepoint
At study enrollment (baseline) and subsequently during regular follow‑up according to the study schedule until the end of the follow‑up period; recurrence or reappearance of cancer will be assessed and recorded at each follow‑up visit (weeks 1 through 10 after treatment initiation, and then at months 3 and 6) through clinical evaluation and periodic imaging at 3 months interval.
Method of measurement
Recurrence will be determined based on standard imaging findings (MRI or CT scan) and clinical assessment, and the date of the event will be recorded.
Intervention groups
1
Description
Intervention group: In this study, patients with hepatocellular carcinoma (HCC) who have undergone successful surgical resection of the liver tumor will receive adjuvant therapy with autologous cytokine‑induced killer (CIK) cells in addition to standard postoperative care.For cell preparation, patients mononuclear cells will be used. Peripheral blood mononuclear cells (PBMCs) are cultured under sterile, Good Manufacturing Practice (GMP) conditions and activated with interferon‑gamma (IFN‑γ), anti‑CD3 antibody, and interleukin‑2 (IL‑2) for approximately 2–3 weeks to generate the effective CIK cell population. After completing culture, the final product undergoes quality control tests for sterility, cell viability, and phenotype. Only products meeting predefined quality criteria will be used for infusion.The CIK cells will be administered through six intravenous infusions — the first three given weekly and the subsequent three every two weeks. Before each infusion, the patient’s clinical condition and basic safety laboratory results (CBC and liver enzymes) will be reviewed. All infusions will be performed in a clinical setting under supervision of the research team, and patients will be monitored for any adverse events or infusion‑related reactions.The objective of this intervention is to evaluate the safety, feasibility, and potential efficacy of adjuvant CIK therapy in reducing disease recurrence following tumor resection in HCC patients.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Liver transplant and surgery research center, Imam Khomeini Hospital, Tehran University of Medical S
Full name of responsible person
Dr. Mohsen Nassiri-Toosi
Street address
East Bagherkhan St. East of Chamran Highway
City
Tehran
Province
Tehran
Postal code
۱۴۱۹۷۳۳۱۴۱
Phone
+98 21 6119 2996
Email
Imamhospital@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Royan Institute
Full name of responsible person
Massoud Vosough
Street address
No, 9, East Shaghayegh Ave, Banihashem St. Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
masvos@yahoo.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Royan Institute
Proportion provided by this source
10
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
2
Sponsor
Name of organization / entity
Bahar Tashkhis Teb
Full name of responsible person
Massoud Vosough
Street address
No 55, Kish Street, Nelson Mandela Street
City
Tehran
Province
Tehran
Postal code
1518835611
Phone
+98 21 8867 6670
Email
info@baharteb.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Bahar Tashkhis Teb
Proportion provided by this source
45
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
3
Sponsor
Name of organization / entity
Kian Immune Cell
Full name of responsible person
Marzieh Ebrahimi
Street address
Unit 13, No. 8, West Shaghayegh Alley, Afshari Str. Banihashem Square, Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665613179
Phone
+98 21 2614 1850
Email
kiacell.immune@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Kian Immune Cell
Proportion provided by this source
45
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
Person responsible for general inquiries
Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Alireza Beheshti Maal
Position
Researcher
Latest degree
Medical doctor
Other areas of specialty/work
Clinical Research Associate
Street address
No 9. East Shaghayegh Alley. Banihashem St. Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
alirezabeheshtimaal@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Massoud Vosough
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Biotechnology
Street address
No 9. East Shaghayegh Alley. Banihashem St. Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
masvos@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Hoda Madani
Position
Researcher
Latest degree
Ph.D.
Other areas of specialty/work
Applied Cell Sciences
Street address
No 9. East Shaghayegh Alley. Banihashem St. Resalat Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
hoda62_m@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available