CholangiocarcinomaPhase 1/2NCT01868490
The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous CIK Cells
A Phase 1/2 study testing cytokine induced killer cells in people with Cholangiocarcinoma and Neuroblastoma, run by Siriraj Hospital at 2 sites in Thailand.
Trial summary
Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the tumors. Read more about this study
- Who is it for?
- Ages 8 to 60 years
- Conditions the study is for
- Cholangiocarcinoma, Neuroblastoma
- What is being tested?
- cytokine induced killer cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesThailand
- Study dates
- 17 Apr 2009to 30 May 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 8 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient must be at least 8 year-old, or allowance from their parent if younger than that.
- Patient must have histologically or cytologically confirmed advanced cholangiocarcinoma or neuroblastoma by oncologist
- The cancers have been failing to current treatment.
- Patient is healthy by getting an Eastern Co-operative Oncology Group (ECOG) performances status of 0, 1 or 2.
- Any of the following lab data
- Hematology:
Show all 15Show fewer
- Hb > 8 g/dl
- Absolute neutrophil count (ANC) > 1,500 cells/mm3
- Absolute lymphocyte count > 1,000 cells/mm3
- Platelet > 100x109/L
- Patient must have a life expectancy of at least 12 weeks by
- Biochemistry:
- Serum total bilirubin < 3 mg/dl
- Serum creatinine < 2 mg/dl
- Patients will comply and provide written informed consent prior to enrollment into the study.
Who cannot join
- Patients received chemotherapy within 4 weeks before study entry.
- Active uncontrolled infection
- Concurrent anti-cancer treatment in another investigational trial, including immunotherapy in last 30 days
- Pregnant or lactating woman, or women of child bearing potential or less than one year after menopause (unless surgically sterile) with urine pregnancy test positive
- Concurrent steroid therapy
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Thailand2 sites
Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok, 10700
Siriraj Clinical Research Center, Siriraj Hospital
Bangkoknoi, Bangkok, 10700
About this study
Official title: Phase 1 Study of The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells.
Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the tumors. Experiments to block the MHC class-I and -II pathways on tumors-RNA transfected DCs showed that only MHC class-I blocking led to a significant reduction of heterogeneous CIK cells cytotoxicity after the co-culture. The safety of CIK cells was demonstrated by the lack of cytotoxicity toward autologous as well as allogeneic normal cells. Co-culture of CIK cells with dendritic cells (DCs) has been reported by us and others in a myriad of cancer (e.g., cholangiocarcinoma, osteosarcoma, glioblastoma multiforme, multiple myeloma, hepatocellular carcinoma, pancreatic carcinoma, renal \& colon carcinoma, murine leukemia \& lymphoma showing enhancement of anti-tumor cytotoxicity of CIK cell in all. The co-culture of CIK cells with DCs were reported to decrease the number of professional regulatory/ suppressor T cells (Treg, CD4+CD25+ cells) and decrease the secretion of IL-10, an immune suppressor cytokine, whereas the cytotoxic activity against target cells increased.
We have recently brought CIK cells through the preclinical phase (animal study) of human cholangiocarcinoma treatment. Cholangiocarcinoma (CCA), is a bile duct epithelial cancer endemic in the Northeast of Thailand, with an increasing incidence discernible in Europe and North America. Conventional treatments including surgery, chemotherapy, and radiation do not bring satisfactory survival due to anatomic location, presence of metastases, and high recurrent rates. These unsatisfactory outcomes urge to search innovative treatments such as immunotherapy. We reported the safety and efficacy of CIK cells in SCID mice model for cholangiocarcinoma. Several conditions of human CIK cells were examined using ex vivo cytotoxic assay and SCID mice pre-inoculated with human cholangiocarcinoma cells. We monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs). Tumor-infiltrating human CD3+ cells were observed from day 2 - 14, but not in normal tissues elsewhere. These altogether indicated the specific homing of CIK cells to tumor mass. All animals did not exhibit any noticeable adverse reaction from the CIK treatments. The CD3+CD56+ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells produced similar efficacy and more feasible for clinical application.
With a complete array of in vitro and in vivo study, the next rational step is moving forward to phase I/II clinical trials for a number of specified solid tumors (i.e., cholangiocarcinoma, osteosarcoma, and glioblastoma multiforme, nueroblastoma) using the optimized autologous CIK cells. Subjects without prior exposure to or weaned for at least 3 months from chemotherapy can be recruited to maintain the integrity of their immunological system, a critical factor for a successful immunotherapy.
- Conditions
- Cholangiocarcinoma, Neuroblastoma
- Being tested
- cytokine induced killer cells
- Keywords
- Cholangiocarcinoma, Cytokine induced killer cells, CIK, Treg, Th17, neuroblastoma
- Medical subject headings
- Cholangiocarcinoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytokine induced killer cellsDrug
at least 10*9 CIK cells, IV on day 0, 14, 28
| Study group | Role | What they receive |
|---|---|---|
| drug | Experimental | single-group studies Receives: Drug: cytokine induced killer cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI scan for monitoring of tumor size and CIK cell-homing, Fluorescence-activated cell sorting (FACS) analysis
Measured: 6 weeks
Secondary outcomes (1)
Survival rate
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study start17 Apr 2009
- Primary completion30 Jan 2028 (estimated)
- Study completion30 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Siriraj Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University
- Responsible party
- Principal investigator, Adisak Wongkajornsilp, Siriraj Hospital
- Investigators
- Adisak Wongkajornsilp, M.D., Ph.D., Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01868490
- Sponsor's protocol ID
- 215-3-2552
- Status last verified
- Feb 2025
- First submitted
- 30 May 2013
- Last updated
- 10 Feb 2025
- Results posted
- No
- 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 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells.
- ClinicalTrials.gov ID
- NCT01868490
- Acronym / sponsor ID
- 215-3-2552
- Conditions
- Cholangiocarcinoma, Neuroblastoma
- Keywords
- Cholangiocarcinoma, Cytokine induced killer cells, CIK, Treg, Th17, neuroblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Siriraj HospitalUniversity, hospital or other
- Collaborators
- Mahidol University
- Study start
- 17 Apr 2009 (actual)
- Primary completion
- 30 Jan 2028 (estimated)
- Study completion
- 30 May 2028 (estimated)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the tumors. Experiments to block the MHC class-I and -II pathways on tumors-RNA transfected DCs showed that only MHC class-I blocking led to a significant reduction of heterogeneous CIK cells cytotoxicity after the co-culture. The safety of CIK cells was demonstrated by the lack of cytotoxicity toward autologous as well as allogeneic normal cells. Co-culture of CIK cells with dendritic cells (DCs) has been reported by us and others in a myriad of cancer (e.g., cholangiocarcinoma, osteosarcoma, glioblastoma multiforme, multiple myeloma, hepatocellular carcinoma, pancreatic carcinoma, renal \& colon carcinoma, murine leukemia \& lymphoma showing enhancement of anti-tumor cytotoxicity of CIK cell in all. The co-culture of CIK cells with DCs were reported to decrease the number of professional regulatory/ suppressor T cells (Treg, CD4+CD25+ cells) and decrease the secretion of IL-10, an immune suppressor cytokine, whereas the cytotoxic activity against target cells increased.
We have recently brought CIK cells through the preclinical phase (animal study) of human cholangiocarcinoma treatment. Cholangiocarcinoma (CCA), is a bile duct epithelial cancer endemic in the Northeast of Thailand, with an increasing incidence discernible in Europe and North America. Conventional treatments including surgery, chemotherapy, and radiation do not bring satisfactory survival due to anatomic location, presence of metastases, and high recurrent rates. These unsatisfactory outcomes urge to search innovative treatments such as immunotherapy. We reported the safety and efficacy of CIK cells in SCID mice model for cholangiocarcinoma. Several conditions of human CIK cells were examined using ex vivo cytotoxic assay and SCID mice pre-inoculated with human cholangiocarcinoma cells. We monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs). Tumor-infiltrating human CD3+ cells were observed from day 2 - 14, but not in normal tissues elsewhere. These altogether indicated the specific homing of CIK cells to tumor mass. All animals did not exhibit any noticeable adverse reaction from the CIK treatments. The CD3+CD56+ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells produced similar efficacy and more feasible for clinical application.
With a complete array of in vitro and in vivo study, the next rational step is moving forward to phase I/II clinical trials for a number of specified solid tumors (i.e., cholangiocarcinoma, osteosarcoma, and glioblastoma multiforme, nueroblastoma) using the optimized autologous CIK cells. Subjects without prior exposure to or weaned for at least 3 months from chemotherapy can be recruited to maintain the integrity of their immunological system, a critical factor for a successful immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| drug | Experimental | Drug: cytokine induced killer cellssingle-group studies |
Who may qualify
- Ages
- 8 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Patient must be at least 8 year-old, or allowance from their parent if younger than that.
- Patient must have histologically or cytologically confirmed advanced cholangiocarcinoma or neuroblastoma by oncologist
- The cancers have been failing to current treatment.
- Patient is healthy by getting an Eastern Co-operative Oncology Group (ECOG) performances status of 0, 1 or 2.
- Any of the following lab data
Key exclusion criteria (5 listed)
- Patients received chemotherapy within 4 weeks before study entry.
- Active uncontrolled infection
- Concurrent anti-cancer treatment in another investigational trial, including immunotherapy in last 30 days
- Pregnant or lactating woman, or women of child bearing potential or less than one year after menopause (unless surgically sterile) with urine pregnancy test positive
- Concurrent steroid therapy
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 |
|---|---|---|
| cytokine induced killer cellsat least 10*9 CIK cells, IV on day 0, 14, 28 | Drug | drug |
Primary outcome
MRI scan for monitoring of tumor size and CIK cell-homing, Fluorescence-activated cell sorting (FACS) analysis
Time frame: 6 weeks
1 secondary outcome
Survival rate
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- 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.
Adisak Wongkajornsilp, M.D., Ph.D. principal investigator
Mahidol University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing cytokine induced killer cells in people with Cholangiocarcinoma and Neuroblastoma, run by Siriraj Hospital at 2 sites in Thailand.
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 15 inclusion and 5 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: enrolling by invitation, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Thailand. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
MRI scan for monitoring of tumor size and CIK cell-homing, Fluorescence-activated cell sorting (FACS) analysis (time frame: 6 weeks). 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 10 Feb 2025; AzTrials last refreshed its copy on 28 Oct 2026.