Hepatocellular CarcinomaPhase 1/2NCT02886897
A Study of Combinations of D-CIK Immunotherapy And Anti-PD-1 In Refractory Solid Tumors
A Phase 1/2 study testing D-CIK and anti-PD-1 antibody in people with Hepatocellular Carcinoma and Renal Cell Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
Background: Combinations of dendritic and cytokine-induced killer cell (D-CIK) based adoptive immunotherapy and anti-PD-1 antibody may enhance the immune response and stop cancer cells from growing. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Renal Cell Carcinoma, Bladder Cancer
- What is being tested?
- D-CIK and anti-PD-1 antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Jul 2016to Oct 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participantswith treatment-refractory advanced hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers.
- Age 18 to 75 years.
- Willing to sign a durable power of attorney.
- Able to understand and sign the Informed Consent Document.
- Life expectancy of greater than three months.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Show all 19Show fewer
- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- Adequate organ function.
- Serology:
- Seronegative for HIV antibody.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- Hematology:
- WBC (> 3000/mm(3)).
- Platelet count greater than 100,000/mm(3).
- Hemoglobin greater than 8.0 g/dl.
- Chemistry:
- Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dl.
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
Who cannot join
- Previous treatment with anti-CTLA-4 and anti-PD-1/PD-L1.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- History of autoimmune disease
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent antineoplastic therapies and systemic steroid therapy.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-Sen University, Cancer Center
Guangzhou, Guangdong, 510060
Jian-Chuan Xia, Ph.D., 86-20-87345699, xiajch@sysucc.org.cn
Fang-jian Zhou, Ph.D., 86-20-87343404, zhoufj@sysucc.org.cn
About this study
Official title: A Phase II Study of Combinations of Dendritic Cells and Cytokine-induced Killer Cell （D-CIK) Immunotherapy And Anti-Programmed Death-1 In Refractory Solid Tumors
Background: Combinations of dendritic and cytokine-induced killer cell (D-CIK) based adoptive immunotherapy and anti-PD-1 antibody may enhance the immune response and stop cancer cells from growing.
Objective: Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and anti-PD-1 antibody in patients with treatment-refractory solid tumors.
Methodology: Phase II clinical trial in patients with advanced metastatic hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers. The D-CIK was isolated from peripheral blood of participants,then activated,expanded and incubated with anti-PD-1 antibody before infusion. The enough number (1.0-1.5 *10^10 cells) of D-CIK were infused back into participants.
Read the detailed description
Heparinized peripheral blood was obtained from participants over a 2-week period. PBMCs were separated by Ficoll-Hypaque gradient centrifugation, suspended in X-VIVO 15 serum-free medium, and culture with 1000 U/ml rhIFN-γfor the first 24 h, followed by stimulation with 100 ng/ml OKT3 , 1000 U/ml rhIL-2 and 100 U/ml IL-1α to activate the CIK.Dendritic cells were incubated with CIK. Fresh medium containing 1000 U/ml rhIL-2 was added every 2 days and the cell density was maintained at 2×10^6 cells/mL.D-CIK were harvested, washed, and resuspended after culture for 14 days. Before cell transfer,D-CIK were incubated with anti-PD-1 antibody,and a fraction of the D-CIK were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous D-CIK (1.0-1.5*10^10 cells) were transferred to patients via intravenous infusion. Generally, participants received at least 4 cycles of treatment at 2-week intervals or received doses until disease progression occurred. If the participants were disease-stable, additional cycles of maintenance treatment were eligible.
Participants will be evaluated for the safety, clinical activity and toxicity. The primary end point was the objective response for each participant at the time of D-CIK and anti-PD-1 infusion as assessed by RECIST. Peripheral blood of patients were also assessed for related cytokine using ELISPOT assays. Additional,the investigators will evaluate tumor markers in participants with clinical response/non-response by immunohistochemical staining of tumor sections from previous diagnostic or therapeutic biopsy samples to determine the predictive biomarker that may be used in future studies.
- Conditions
- Hepatocellular Carcinoma, Renal Cell Carcinoma, Bladder Cancer, Colorectal Cancer, Non-small-cell Lung Cancer, Breast Cancer
- Being tested
- D-CIK and anti-PD-1 antibody
- Keywords
- Refractory solid tumors, Dendritic and Cytokine-induced killer cell, Anti-PD-1 antibody, Combination immunotherapy
- Medical subject headings
- Carcinoma, Hepatocellular, Carcinoma, Renal Cell, Urinary Bladder Neoplasms, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-CIK and anti-PD-1 antibodyBiological
Autologous dendritic and cytokine-induced killer cells (D-CIK)(1.0-1.5*10^10 cells)were incubated with anti-PD-1 antibody and infused into participants.
| Study group | Role | What they receive |
|---|---|---|
| D-CIK and anti-PD-1 Immunotherapy | Experimental | D-CIK was incubated with anti-PD-1 antibody before infused back into participants Receives: Biological: D-CIK and anti-PD-1 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress-free survival(PFS)
PFS is defined as the time from the combined therapy until objective tumor progression or death.
Measured: 12 Months
Secondary outcomes (4)
Overall survival (OS)
OS is defined as the time from the combined therapy until death from any cause
Measured: 12 Months
Laboratory findings
The number and secreted cytokines of CD3+ (or CD8+ or CD4+ or CD56+) T cells
Measured: 6 Months
Objective response rate
The total number of Complete remission and Partial remission (According to the response criteria in solid tumor(RECIST))
Measured: 12 Months
Severity of adverse events
According to National Cancer Institute Common Terminology Criteria for Adverse Events（NCI-CTCAE)
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 posted1 Sep 2016 (estimated)
- Study startJul 2016
- Primary completionSep 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianchuan Xia, Sun Yat-sen University
- Investigators
- Yi-Xin Zeng, Ph.D., Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02886897
- Sponsor's protocol ID
- B2016-036-01
- Status last verified
- Aug 2016
- First submitted
- 14 Aug 2016
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012 Mar 28;4(127):127ra37. doi: 10.1126/scitranslmed.3003689.
PubMed 22461641Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
PubMed 25747273Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015 Aug;14(8):561-84. doi: 10.1038/nrd4591.
PubMed 26228759Pan K, Guan XX, Li YQ, Zhao JJ, Li JJ, Qiu HJ, Weng DS, Wang QJ, Liu Q, Huang LX, He J, Chen SP, Ke ML, Zeng YX, Xia JC. Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in patients with post-mastectomy triple-negative breast cancer. Clin Cancer Res. 2014 Jun 1;20(11):3003-11. doi: 10.1158/1078-0432.CCR-14-0082. Epub 2014 Mar 25.
PubMed 24668644Dai C, Lin F, Geng R, Ge X, Tang W, Chang J, Wu Z, Liu X, Lin Y, Zhang Z, Li J. Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer. Oncotarget. 2016 Mar 1;7(9):10332-44. doi: 10.18632/oncotarget.7243.
PubMed 26871284
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Combinations of Dendritic Cells and Cytokine-induced Killer Cell （D-CIK) Immunotherapy And Anti-Programmed Death-1 In Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT02886897
- Acronym / sponsor ID
- B2016-036-01
- Conditions
- Hepatocellular Carcinoma, Renal Cell Carcinoma, Bladder Cancer, Colorectal Cancer, Non-small-cell Lung Cancer, Breast Cancer
- Keywords
- Refractory solid tumors, Dendritic and Cytokine-induced killer cell, Anti-PD-1 antibody, Combination immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Jul 2016
- Primary completion
- Sep 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 1 Sep 2016 (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.
Background: Combinations of dendritic and cytokine-induced killer cell (D-CIK) based adoptive immunotherapy and anti-PD-1 antibody may enhance the immune response and stop cancer cells from growing.
Objective: Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and anti-PD-1 antibody in patients with treatment-refractory solid tumors.
Methodology: Phase II clinical trial in patients with advanced metastatic hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers. The D-CIK was isolated from peripheral blood of participants,then activated,expanded and incubated with anti-PD-1 antibody before infusion. The enough number (1.0-1.5 *10^10 cells) of D-CIK were infused back into participants.
Detailed description
Heparinized peripheral blood was obtained from participants over a 2-week period. PBMCs were separated by Ficoll-Hypaque gradient centrifugation, suspended in X-VIVO 15 serum-free medium, and culture with 1000 U/ml rhIFN-γfor the first 24 h, followed by stimulation with 100 ng/ml OKT3 , 1000 U/ml rhIL-2 and 100 U/ml IL-1α to activate the CIK.Dendritic cells were incubated with CIK. Fresh medium containing 1000 U/ml rhIL-2 was added every 2 days and the cell density was maintained at 2×10^6 cells/mL.D-CIK were harvested, washed, and resuspended after culture for 14 days. Before cell transfer,D-CIK were incubated with anti-PD-1 antibody,and a fraction of the D-CIK were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous D-CIK (1.0-1.5*10^10 cells) were transferred to patients via intravenous infusion. Generally, participants received at least 4 cycles of treatment at 2-week intervals or received doses until disease progression occurred. If the participants were disease-stable, additional cycles of maintenance treatment were eligible.
Participants will be evaluated for the safety, clinical activity and toxicity. The primary end point was the objective response for each participant at the time of D-CIK and anti-PD-1 infusion as assessed by RECIST. Peripheral blood of patients were also assessed for related cytokine using ELISPOT assays. Additional,the investigators will evaluate tumor markers in participants with clinical response/non-response by immunohistochemical staining of tumor sections from previous diagnostic or therapeutic biopsy samples to determine the predictive biomarker that may be used in future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| D-CIK and anti-PD-1 Immunotherapy | Experimental | Biological: D-CIK and anti-PD-1 antibodyD-CIK was incubated with anti-PD-1 antibody before infused back into participants |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participantswith treatment-refractory advanced hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers.
- Age 18 to 75 years.
- Willing to sign a durable power of attorney.
- Able to understand and sign the Informed Consent Document.
- Life expectancy of greater than three months.
Key exclusion criteria (6 listed)
- Previous treatment with anti-CTLA-4 and anti-PD-1/PD-L1.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- History of autoimmune disease
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
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 |
|---|---|---|
| D-CIK and anti-PD-1 antibodyAutologous dendritic and cytokine-induced killer cells (D-CIK)(1.0-1.5*10^10 cells)were incubated with anti-PD-1 antibody and infused into participants. | Biological | D-CIK and anti-PD-1 Immunotherapy |
Primary outcome
Progress-free survival(PFS)
Time frame: 12 Months
PFS is defined as the time from the combined therapy until objective tumor progression or death.
4 secondary outcomes
Overall survival (OS)
Time frame: 12 Months
Laboratory findings
Time frame: 6 Months
Objective response rate
Time frame: 12 Months
Severity of adverse events
Time frame: 12 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Results publication: PubMed 22461641Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012 Mar 28;4(127):127ra37. doi: 10.1126/scitranslmed.3003689.
- Results publication: PubMed 25747273Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
- Results publication: PubMed 26228759Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015 Aug;14(8):561-84. doi: 10.1038/nrd4591.
- Results publication: PubMed 24668644Pan K, Guan XX, Li YQ, Zhao JJ, Li JJ, Qiu HJ, Weng DS, Wang QJ, Liu Q, Huang LX, He J, Chen SP, Ke ML, Zeng YX, Xia JC. Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in patients with post-mastectomy triple-negative breast cancer. Clin Cancer Res. 2014 Jun 1;20(11):3003-11. doi: 10.1158/1078-0432.CCR-14-0082. Epub 2014 Mar 25.
- Results publication: PubMed 26871284Dai C, Lin F, Geng R, Ge X, Tang W, Chang J, Wu Z, Liu X, Lin Y, Zhang Z, Li J. Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer. Oncotarget. 2016 Mar 1;7(9):10332-44. doi: 10.18632/oncotarget.7243.
- Individual participant dataSharing planned: Undecided
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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.
Yi-Xin Zeng, Ph.D. principal investigator
Sun Yat-sen University
1 site 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 D-CIK and anti-PD-1 antibody in people with Hepatocellular Carcinoma and Renal Cell Carcinoma, run by Sun Yat-sen University 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 19 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 1 Sep 2016. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jian-Chuan Xia, Ph.D. (862087345699, xiajch@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress-free survival(PFS) (time frame: 12 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02886897, which also lists 5 linked publications.
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 1 Sep 2016.