Immunotherapy Using Precision T Cells Specific to Personalized Neo-antigen for the Treatment of Advanced Malignant Tumor of Biliary Tract
NCT ID: NCT02632019
Last Updated: 2016-01-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE1/PHASE2
40 participants
INTERVENTIONAL
2015-09-30
2017-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The purpose of this study is to evaluate the safety and prognosis of dendritic cell-precision T cell for neo-antigen in the treatment of advanced biliary tract malignant tumor.
Methods:
This study designs a novel therapy using dendritic cell-precision multiple antigen T cells. 40 patients will be enrolled. They are randomly divided into gemcitabine group and dendritic cell-precision T cell for neo-antigen combined with gemcitabine group. Gemcitabine treatments will be performed once a week with a total of six times. Dendritic cell-precision T cell for neo-antigen combined with gemcitabine treatment: Gemcitabine: once a week with a total of six times before 60 days prior to the start of drawing blood. Dendritic cell-precision T cell for neo-antigen: once per 3 weeks with a total of three periods. The mail clinical indicators are Progression-Free-Survival and Overall Survival.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Evaluate the Efficacy and Safety of Activated T-lymphocyte Cell Therapy in Advanced Pancreatic Cancer
NCT00965718
Clinical Efficacy and Safety of Dendritic Cytotoxic Lymphocyte(DC-CTL) Cell Infusion in NSCLC Patients
NCT02766348
Personalized Immune Cell Therapy Targeting Neoantigen of Malignant Solid Tumors
NCT05235607
Immune Cell Therapy for Advanced Solid Tumors
NCT07260058
Clinical Efficacy and Safety of NKT Cell Infusion in Patients With Advanced Solid Tumor
NCT02562963
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
gemcitabine
Gemcitabine treatments will be performed once a week with a total of six times
Gemcitabine
Gemcitabine 1000mg/m2, Physiological saline 100ml:IV (in the vein) once a week with a total of six times.
Dendritic cell-precision T cell for neo-antigen
Dendritic cell-precision T cell for neo-antigen (DC-PNAT) combined with gemcitabine treatment: Gemcitabine: once a week with a total of six times before 60 days prior to the start of drawing blood. DC-PNAT: once per 3 weeks with a total of three periods.
Gemcitabine
Gemcitabine 1000mg/m2, Physiological saline 100ml:IV (in the vein) once a week with a total of six times.
Dendritic cell-precision T cell for neo-antigen combined with gemcitabine treatment
Gemcitabine: Gemcitabine 1000mg/m2, Physiological saline 100ml: IV (in the vein) once a week with a total of six times before 60 days prior to the start of drawing blood. DC-PNAT: DC cell suspension (1×107 DC+ physiological saline + 0.25% human serum albumin) 1ml for each infusion, subcutaneous injection for each infusion, 3 cycles, each cycle received two infusions on day 19, 20; 40, 41; 61, 62.
PNAT cell suspension (1-6×109 PNAT + physiological saline + 0.25% human serum albumin) 300ml for each infusion, IV (in the vein) for each infusion, 3 cycles, each cycle received one infusions on day 21, 42, 63.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Gemcitabine
Gemcitabine 1000mg/m2, Physiological saline 100ml:IV (in the vein) once a week with a total of six times.
Dendritic cell-precision T cell for neo-antigen combined with gemcitabine treatment
Gemcitabine: Gemcitabine 1000mg/m2, Physiological saline 100ml: IV (in the vein) once a week with a total of six times before 60 days prior to the start of drawing blood. DC-PNAT: DC cell suspension (1×107 DC+ physiological saline + 0.25% human serum albumin) 1ml for each infusion, subcutaneous injection for each infusion, 3 cycles, each cycle received two infusions on day 19, 20; 40, 41; 61, 62.
PNAT cell suspension (1-6×109 PNAT + physiological saline + 0.25% human serum albumin) 300ml for each infusion, IV (in the vein) for each infusion, 3 cycles, each cycle received one infusions on day 21, 42, 63.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Exclusion Criteria
18 Years
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Second Military Medical University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Xiaoqing Jiang, MD
Role: STUDY_CHAIR
Eastern Hepatobiliary Surgery Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Eastern Hepatobiliary Surgery Hospital
Shanghai, , China
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Curtsinger JM, Mescher MF. Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol. 2010 Jun;22(3):333-40. doi: 10.1016/j.coi.2010.02.013. Epub 2010 Apr 2.
Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P. Human T cell responses against melanoma. Annu Rev Immunol. 2006;24:175-208. doi: 10.1146/annurev.immunol.24.021605.090733.
Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701-2. doi: 10.1038/248701a0. No abstract available.
Lafferty KJ, Warren HS, Woolnough JA. A mediator acting as a costimulator for the development of cytotoxic responses in vitro. Adv Exp Med Biol. 1979;114:497-501. doi: 10.1007/978-1-4615-9101-6_82. No abstract available.
Turtle CJ, Hudecek M, Jensen MC, Riddell SR. Engineered T cells for anti-cancer therapy. Curr Opin Immunol. 2012 Oct;24(5):633-9. doi: 10.1016/j.coi.2012.06.004. Epub 2012 Jul 18.
Lee PP, Yee C, Savage PA, Fong L, Brockstedt D, Weber JS, Johnson D, Swetter S, Thompson J, Greenberg PD, Roederer M, Davis MM. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med. 1999 Jun;5(6):677-85. doi: 10.1038/9525.
Radoja S, Saio M, Frey AB. CD8+ tumor-infiltrating lymphocytes are primed for Fas-mediated activation-induced cell death but are not apoptotic in situ. J Immunol. 2001 May 15;166(10):6074-83. doi: 10.4049/jimmunol.166.10.6074.
Radoja S, Saio M, Schaer D, Koneru M, Vukmanovic S, Frey AB. CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol. 2001 Nov 1;167(9):5042-51. doi: 10.4049/jimmunol.167.9.5042.
Driessens G, Kline J, Gajewski TF. Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev. 2009 May;229(1):126-44. doi: 10.1111/j.1600-065X.2009.00771.x.
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006 Oct 6;314(5796):126-9. doi: 10.1126/science.1129003. Epub 2006 Aug 31.
Santarpia M, Karachaliou N. Tumor immune microenvironment characterization and response to anti-PD-1 therapy. Cancer Biol Med. 2015 Jun;12(2):74-8. doi: 10.7497/j.issn.2095-3941.2015.0022. No abstract available.
Nagaraj S, Gabrilovich DI. Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res. 2008 Apr 15;68(8):2561-3. doi: 10.1158/0008-5472.CAN-07-6229.
Staveley-O'Carroll K, Sotomayor E, Montgomery J, Borrello I, Hwang L, Fein S, Pardoll D, Levitsky H. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1178-83. doi: 10.1073/pnas.95.3.1178.
Ilyas SI, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013 Dec;145(6):1215-29. doi: 10.1053/j.gastro.2013.10.013. Epub 2013 Oct 15.
Bergquist A, von Seth E. Epidemiology of cholangiocarcinoma. Best Pract Res Clin Gastroenterol. 2015 Apr;29(2):221-32. doi: 10.1016/j.bpg.2015.02.003. Epub 2015 Feb 16.
Cai XY, Gao Q, Qiu SJ, Ye SL, Wu ZQ, Fan J, Tang ZY. Dendritic cell infiltration and prognosis of human hepatocellular carcinoma. J Cancer Res Clin Oncol. 2006 May;132(5):293-301. doi: 10.1007/s00432-006-0075-y. Epub 2006 Jan 19.
Knippertz I, Hesse A, Schunder T, Kampgen E, Brenner MK, Schuler G, Steinkasserer A, Nettelbeck DM. Generation of human dendritic cells that simultaneously secrete IL-12 and have migratory capacity by adenoviral gene transfer of hCD40L in combination with IFN-gamma. J Immunother. 2009 Jun;32(5):524-38. doi: 10.1097/CJI.0b013e3181a28422.
Bonehill A, Van Nuffel AM, Corthals J, Tuyaerts S, Heirman C, Francois V, Colau D, van der Bruggen P, Neyns B, Thielemans K. Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients. Clin Cancer Res. 2009 May 15;15(10):3366-75. doi: 10.1158/1078-0432.CCR-08-2982. Epub 2009 May 5.
Bellik L, Gerlini G, Parenti A, Ledda F, Pimpinelli N, Neri B, Pantalone D. Role of conventional treatments on circulating and monocyte-derived dendritic cells in colorectal cancer. Clin Immunol. 2006 Oct;121(1):74-80. doi: 10.1016/j.clim.2006.06.011. Epub 2006 Aug 17.
Babatz J, Rollig C, Lobel B, Folprecht G, Haack M, Gunther H, Kohne CH, Ehninger G, Schmitz M, Bornhauser M. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. Cancer Immunol Immunother. 2006 Mar;55(3):268-76. doi: 10.1007/s00262-005-0021-x. Epub 2005 Jul 21.
Fay JW, Palucka AK, Paczesny S, Dhodapkar M, Johnston DA, Burkeholder S, Ueno H, Banchereau J. Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34(+) progenitor-derived dendritic cells. Cancer Immunol Immunother. 2006 Oct;55(10):1209-18. doi: 10.1007/s00262-005-0106-6. Epub 2005 Dec 6.
Davis ID, Chen Q, Morris L, Quirk J, Stanley M, Tavarnesi ML, Parente P, Cavicchiolo T, Hopkins W, Jackson H, Dimopoulos N, Tai TY, MacGregor D, Browning J, Svobodova S, Caron D, Maraskovsky E, Old LJ, Chen W, Cebon J. Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients. J Immunother. 2006 Sep-Oct;29(5):499-511. doi: 10.1097/01.cji.0000211299.29632.8c.
Escobar A, Lopez M, Serrano A, Ramirez M, Perez C, Aguirre A, Gonzalez R, Alfaro J, Larrondo M, Fodor M, Ferrada C, Salazar-Onfray F. Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients. Clin Exp Immunol. 2005 Dec;142(3):555-68. doi: 10.1111/j.1365-2249.2005.02948.x.
Thomas-Kaskel AK, Zeiser R, Jochim R, Robbel C, Schultze-Seemann W, Waller CF, Veelken H. Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival. Int J Cancer. 2006 Nov 15;119(10):2428-34. doi: 10.1002/ijc.22097.
Fuessel S, Meye A, Schmitz M, Zastrow S, Linne C, Richter K, Lobel B, Hakenberg OW, Hoelig K, Rieber EP, Wirth MP. Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Prostate. 2006 Jun 1;66(8):811-21. doi: 10.1002/pros.20404.
Kyte JA, Gaudernack G. Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells. Cancer Immunol Immunother. 2006 Nov;55(11):1432-42. doi: 10.1007/s00262-006-0161-7. Epub 2006 Apr 13.
Wang QJ, Hanada K, Perry-Lalley D, Bettinotti MP, Karpova T, Khong HT, Yang JC. Generating renal cancer-reactive T cells using dendritic cells (DCs) to present autologous tumor. J Immunother. 2005 Nov-Dec;28(6):551-9. doi: 10.1097/01.cji.0000175495.13476.1f.
Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, Nussbaumer W, Falkensammer C, Bartsch G, Thurnher M. Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother. 2005 Jul;54(7):663-70. doi: 10.1007/s00262-004-0629-2. Epub 2004 Dec 17.
Ferrari S, Malugani F, Rovati B, Porta C, Riccardi A, Danova M. Flow cytometric analysis of circulating dendritic cell subsets and intracellular cytokine production in advanced breast cancer patients. Oncol Rep. 2005 Jul;14(1):113-20.
Bohnenkamp HR, Coleman J, Burchell JM, Taylor-Papadimitriou J, Noll T. Breast carcinoma cell lysate-pulsed dendritic cells cross-prime MUC1-specific CD8+ T cells identified by peptide-MHC-class-I tetramers. Cell Immunol. 2004 Sep-Oct;231(1-2):112-25. doi: 10.1016/j.cellimm.2004.12.007. Epub 2005 Feb 8.
Chen W, Chan AS, Dawson AJ, Liang X, Blazar BR, Miller JS. FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides to enhance T-cell and natural killer cell function. Biol Blood Marrow Transplant. 2005 Jan;11(1):23-34. doi: 10.1016/j.bbmt.2004.08.004.
Triozzi PL, Khurram R, Aldrich WA, Walker MJ, Kim JA, Jaynes S. Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer. Cancer. 2000 Dec 15;89(12):2646-54. doi: 10.1002/1097-0142(20001215)89:123.0.co;2-a.
Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. doi: 10.1038/nature13904.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014 Nov 27;515(7528):568-71. doi: 10.1038/nature13954.
Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber WJ, Mulder GE, Toebes M, Vesely MD, Lam SS, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee HG, Melief CJ, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014 Nov 27;515(7528):577-81. doi: 10.1038/nature13988.
Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, Franci C, Cheung TK, Fritsche J, Weinschenk T, Modrusan Z, Mellman I, Lill JR, Delamarre L. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014 Nov 27;515(7528):572-6. doi: 10.1038/nature14001.
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.
Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56-61. doi: 10.1126/science.aaa8172.
Fischbach MA, Bluestone JA, Lim WA. Cell-based therapeutics: the next pillar of medicine. Sci Transl Med. 2013 Apr 3;5(179):179ps7. doi: 10.1126/scitranslmed.3005568.
Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62-8. doi: 10.1126/science.aaa4967.
Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015 Apr 3;348(6230):69-74. doi: 10.1126/science.aaa4971.
Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013 Jun;19(6):747-52. doi: 10.1038/nm.3161. Epub 2013 May 5.
Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
EHBHKY2015-02-006
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.