- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02886897
A Study of Combinations of D-CIK Immunotherapy And Anti-PD-1 In Refractory Solid Tumors
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jian-Chuan Xia, Ph.D.
- Phone Number: 862087345699
- Email: xiajch@sysucc.org.cn
Study Contact Backup
- Name: Yi-Xin Zeng, Ph.D.
- Phone Number: 862087343333
- Email: zengYX@sysucc.org.cn
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510060
- Recruiting
- Sun Yat-sen University, Cancer Center
-
Contact:
- Fang-jian Zhou, Ph.D.
- Phone Number: 86-20-87343404
- Email: zhoufj@sysucc.org.cn
-
Principal Investigator:
- Yi-Xin Zeng, Ph.D.
-
Sub-Investigator:
- Fang-jian Zhou, Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: D-CIK and anti-PD-1 Immunotherapy
D-CIK was incubated with anti-PD-1 antibody before infused back into participants
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progress-free survival(PFS)
Time Frame: 12 Months
|
PFS is defined as the time from the combined therapy until objective tumor progression or death.
|
12 Months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: 12 Months
|
OS is defined as the time from the combined therapy until death from any cause
|
12 Months
|
Laboratory findings
Time Frame: 6 Months
|
The number and secreted cytokines of CD3+ (or CD8+ or CD4+ or CD56+) T cells
|
6 Months
|
Objective response rate
Time Frame: 12 Months
|
The total number of Complete remission and Partial remission (According to the response criteria in solid tumor(RECIST))
|
12 Months
|
Severity of adverse events
Time Frame: 12 Months
|
According to National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE)
|
12 Months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Yi-Xin Zeng, Ph.D., Sun Yat-sen University
Publications and helpful links
General 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.
- Lee 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.
- Mahoney 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.
- Pan 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.
- Dai 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- B2016-036-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Renal Cell Carcinoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Australian and New Zealand Urogenital and Prostate...RecruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11.2 Translocation-Related Renal Cell CarcinomaAustralia
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell CarcinomaUnited States
-
Bradley A. McGregor, MDBristol-Myers Squibb; ExelixisRecruitingRenal Cell Carcinoma | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Collecting Duct Renal Cell Carcinoma | Translocation Renal Cell Carcinoma | Unresectable Advanced Renal Cell Carcinoma | Metastatic Ncc Renal Cell CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell CarcinomaUnited States, Taiwan, Australia
-
Jonsson Comprehensive Cancer CenterBeiGene; Driven To CureWithdrawnMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8 | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Unresectable Renal Cell Carcinoma | Hereditary Leiomyomatosis and Renal Cell Carcinoma | Clear Cell Papillary Renal Neoplasm | Hereditary Papillary Renal Cell Carcinoma and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingChromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma | Fumarate Hydratase Deficient Renal Cell Carcinoma | Succinate Dehydrogenase Deficient Renal Cell Carcinoma | Collecting Duct Renal...United States
-
Australian and New Zealand Urogenital and Prostate...Bristol-Myers SquibbActive, not recruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11 Translocation CarcinomaAustralia
-
National Cancer Institute (NCI)Canadian Cancer Trials GroupActive, not recruitingUnresectable Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v7 | Stage IV Renal Cell Cancer AJCC v7 | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell Carcinoma | Metastatic Papillary Renal Cell Carcinoma | Locally Advanced Papillary Renal Cell CarcinomaUnited States, Canada
-
Peloton Therapeutics, Inc.Active, not recruitingKidney Cancer | Renal Cell Carcinoma | Renal Cancer | Renal Cell Carcinoma (RCC) | Renal Cell Cancer Metastatic | Kidney | Clear Cell Renal Cell Carcinoma (ccRCC) | Renal Cell Carcinoma Recurrent | Renal Cell Cancer, RecurrentUnited States
Clinical Trials on D-CIK and anti-PD-1 antibody
-
Capital Medical UniversityDuke UniversityCompleted
-
Capital Medical UniversityDuke University; Geneplus-Beijing Co. Ltd.CompletedNeoplasms | Lung CancerChina
-
Dalian UniversityUnknownNon-small Cell Lung Cancer
-
Capital Medical UniversityTerminatedCancer | Mesothelioma, MalignantChina
-
Allife Medical Science and Technology Co., Ltd.Beijing Hospital; The First People's Hospital of Yunnan Province/First People... and other collaboratorsUnknown
-
Beijing Tongren HospitalNot yet recruitingExtranodal NK/T-cell Lymphoma, Nasal Type
-
Tianjin Medical University Cancer Institute and...Jiangsu HengRui Medicine Co., Ltd.Completed
-
Nanjing Leads Biolabs Co.,LtdRecruitingAdvanced Malignant TumorsChina
-
Henlix, IncUnknown
-
Zhujiang HospitalNot yet recruitingHepatocellular Carcinoma Non-resectable