Cancer Immune Therapy for the Treatment of Refractory Solid Tumours of Childhood
NCT ID: NCT02533895
Last Updated: 2015-12-29
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.
COMPLETED
PHASE1
67 participants
INTERVENTIONAL
2000-02-29
2015-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a long-term (LT) follow-up investigation of the 14 sarcoma patients, which will be treated using the AV0113 Dendritic Cell Cancer Immune Therapy (DC-CIT) technology is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.
Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 historic control sarcoma patients that will be matched for disease, recurrences, relapses etc.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Peripheral blood mononuclear cells (MNCs) will be obtained from patients by leukocyte apheresis. Monocytes enriched by density gradient centrifugation from MNCs will be used to generate immature DCs by cultivation in recombinant human interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating-factor (GM-CSF). These immature DCs will be loaded with autologous tumour cell lysates obtained by needle biopsy or surgery prior to tumour vaccination.The antigen loaded immature DCs will then receive a final maturation stimulus transmitted by exposure to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Maturation enables DCs to present antigen with high efficiency to T-lymphocytes. Subsequently, mature loaded DCs will be injected subcutaneously close to tumour free lymph nodes or intra-nodally into tumour free lymph nodes at weekly intervals for at least 6 weeks.
It is anticipated to establish the feasibility and safety of tumour vaccination in the described clinical setting and to find some clinical and/or experimental evidence for the induction of an anti-tumour immune response.
For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a long-term (LT) follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.
Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 historic control sarcoma patients that will be matched for disease, recurrences, relapses etc.
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.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment with AV0113
14 sarcoma and 7 non-sarcoma are treated with AV0113, an anti-tumour immune therapy with autologous DCs loaded with tumour cell lysates in order to establish the feasibility and safety of tumour vaccination.
Peripheral blood mononuclear cells (MNCs) are obtained from patients by leukocyte apheresis. Monocytes enriched by density gradient centrifugation from MNCs will be used to generate immature DCs. These immature DCs will be loaded with autologous tumour cell lysates obtained by needle biopsy or surgery prior to tumour vaccination. The antigen loaded immature DCs will then receive a final maturation stimulus transmitted by exposure to lipopolysaccharide and interferon-gamma. Maturation enables DCs to present antigen with high efficiency to T-lymphocytes.
AV0113 DC-CIT
Mature loaded DCs will be injected intra-nodally into tumour free lymph nodes or subcutaneously close to tumour free lymph nodes at weekly intervals for at least 6 weeks.
Data evaluation
For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a LT follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology, is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.
Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 control sarcoma patients that will be matched for disease, recurrences, relapses etc
Historic control
In order to be able to compare the survival data of 14 sarcoma patients treated with AV0113, 42 historic control sarcoma patients from the data base of the Department of Orthopaedics, Medical University Vienna, that will be matched for disease, recurrences, relapses etc. will be included into this study.
Data evaluation
For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a LT follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology, is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.
Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 control sarcoma patients that will be matched for disease, recurrences, relapses etc
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AV0113 DC-CIT
Mature loaded DCs will be injected intra-nodally into tumour free lymph nodes or subcutaneously close to tumour free lymph nodes at weekly intervals for at least 6 weeks.
Data evaluation
For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a LT follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology, is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.
Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 control sarcoma patients that will be matched for disease, recurrences, relapses etc
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must not be HIV-positive.
* Patients must have primary tumour tissue or cells available at sufficient number to allow treatment according to the protocol.
* Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
* Patients suffering from bone or soft tissue sarcoma that received treatment with AV0113 or are documented in the database of the Medical University Vienna's Department of Orthopaedics.
* At least one disease recurrence after first CR or worse disease condition (e.g.: never reached CR).
* Diagnosis between 1992-2003 and/or "inclusion time point" during the years 2000-2004.
* Availability of date of death or of confirmation that patient is still alive (for the currentness of confirmation that patients are still alive only the time span from 1 April 2014 to 1 April 2015 is accepted).
* Patients not older than 27 years at their ITP.
* Any condition which, in the investigator's opinion, may pose a risk to the patient or will interfere with the study objectives.
Exclusion Criteria
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Activartis Biotech
INDUSTRY
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.
Reinhard Windhager, Dr.
Role: STUDY_DIRECTOR
Department of Orthopaedics, Medical University Vienna
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Department of Orthopaedics, Medical University Vienna
Vienna, , Austria
St. Anna Children's Hospital
Vienna, , Austria
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bleyer WA. The impact of childhood cancer on the United States and the world. CA Cancer J Clin. 1990 Nov-Dec;40(6):355-67. doi: 10.3322/canjclin.40.6.355. No abstract available.
Cheung NK. Immunotherapy. Neuroblastoma as a model. Pediatr Clin North Am. 1991 Apr;38(2):425-41. doi: 10.1016/s0031-3955(16)38085-3.
Mayer P, Handgretinger R, Bruchelt G, Schaber B, Rassner G, Fierlbeck G. Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a. Melanoma Res. 1994 Apr;4(2):101-6. doi: 10.1097/00008390-199404000-00004.
Cheung NK, Lazarus H, Miraldi FD, Abramowsky CR, Kallick S, Saarinen UM, Spitzer T, Strandjord SE, Coccia PF, Berger NA. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol. 1987 Sep;5(9):1430-40. doi: 10.1200/JCO.1987.5.9.1430.
Handgretinger R, Baader P, Dopfer R, Klingebiel T, Reuland P, Treuner J, Reisfeld RA, Niethammer D. A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother. 1992;35(3):199-204. doi: 10.1007/BF01756188.
Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, Kasi LP, Bhadkamkar V, Fritsche HA, Benjamin RS, et al. Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol. 1994 Jan;12(1):184-93. doi: 10.1200/JCO.1994.12.1.184.
Khanna C, Anderson PM, Hasz DE, Katsanis E, Neville M, Klausner JS. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer. 1997 Apr 1;79(7):1409-21. doi: 10.1002/(sici)1097-0142(19970401)79:73.0.co;2-3.
Sinkovics JG, Horvath JC. Vaccination against human cancers (review). Int J Oncol. 2000 Jan;16(1):81-96. doi: 10.3892/ijo.16.1.81.
Pardoll DM. Inducing autoimmune disease to treat cancer. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5340-2. doi: 10.1073/pnas.96.10.5340. No abstract available.
Roskrow MA, Dilloo D, Suzuki N, Zhong W, Rooney CM, Brenner MK. Autoimmune disease induced by dendritic cell immunization against leukemia. Leuk Res. 1999 Jun;23(6):549-57. doi: 10.1016/s0145-2126(99)00045-4.
Darnell RB, DeAngelis LM. Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet. 1993 Jan 2;341(8836):21-2. doi: 10.1016/0140-6736(93)92485-c.
Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4529-36. doi: 10.1073/pnas.93.10.4529.
Connolly AM, Pestronk A, Mehta S, Pranzatelli MR 3rd, Noetzel MJ. Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: an analysis of antigenic targets in neural tissues. J Pediatr. 1997 Jun;130(6):878-84. doi: 10.1016/s0022-3476(97)70272-5.
Aichele P, Kyburz D, Ohashi PS, Odermatt B, Zinkernagel RM, Hengartner H, Pircher H. Peptide-induced T-cell tolerance to prevent autoimmune diabetes in a transgenic mouse model. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):444-8. doi: 10.1073/pnas.91.2.444.
Aichele P, Brduscha-Riem K, Zinkernagel RM, Hengartner H, Pircher H. T cell priming versus T cell tolerance induced by synthetic peptides. J Exp Med. 1995 Jul 1;182(1):261-6. doi: 10.1084/jem.182.1.261.
Takahashi H, Takeshita T, Morein B, Putney S, Germain RN, Berzofsky JA. Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature. 1990 Apr 26;344(6269):873-5. doi: 10.1038/344873a0.
Toes RE, Offringa R, Blom RJ, Melief CJ, Kast WM. Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7855-60. doi: 10.1073/pnas.93.15.7855.
Toes RE, Blom RJ, Offringa R, Kast WM, Melief CJ. Enhanced tumor outgrowth after peptide vaccination. Functional deletion of tumor-specific CTL induced by peptide vaccination can lead to the inability to reject tumors. J Immunol. 1996 May 15;156(10):3911-8.
Medzhitov R, Janeway CA Jr. Decoding the patterns of self and nonself by the innate immune system. Science. 2002 Apr 12;296(5566):298-300. doi: 10.1126/science.1068883.
Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol. 2000 Oct;1(4):311-6. doi: 10.1038/79758.
Felzmann T, Huttner KG, Breuer SK, Wimmer D, Ressmann G, Wagner D, Paul P, Lehner M, Heitger A, Holter W. Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses. Cancer Immunol Immunother. 2005 Aug;54(8):769-80. doi: 10.1007/s00262-004-0637-2. Epub 2005 Jan 13.
Huttner KG, Breuer SK, Paul P, Majdic O, Heitger A, Felzmann T. Generation of potent anti-tumor immunity in mice by interleukin-12-secreting dendritic cells. Cancer Immunol Immunother. 2005 Jan;54(1):67-77. doi: 10.1007/s00262-004-0571-3.
Dohnal AM, Graffi S, Witt V, Eichstill C, Wagner D, Ul-Haq S, Wimmer D, Felzmann T. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines. J Cell Mol Med. 2009 Jan;13(1):125-35. doi: 10.1111/j.1582-4934.2008.00304.x. Epub 2008 Mar 17.
Dohnal AM, Witt V, Hugel H, Holter W, Gadner H, Felzmann T. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy. 2007;9(8):755-70. doi: 10.1080/14653240701589221. Epub 2007 Oct 4.
Traxlmayr MW, Wesch D, Dohnal AM, Funovics P, Fischer MB, Kabelitz D, Felzmann T. Immune suppression by gammadelta T-cells as a potential regulatory mechanism after cancer vaccination with IL-12 secreting dendritic cells. J Immunother. 2010 Jan;33(1):40-52. doi: 10.1097/CJI.0b013e3181b51447.
Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med. 2000 Nov 6;192(9):1213-22. doi: 10.1084/jem.192.9.1213.
Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science. 2002 Sep 13;297(5588):1867-70. doi: 10.1126/science.1073514.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol. 1997 Dec;27(12):3135-42. doi: 10.1002/eji.1830271209.
ESMO / European Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct;23 Suppl 7:vii100-9. doi: 10.1093/annonc/mds254. No abstract available.
Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev. 2006 Oct;32(6):423-36. doi: 10.1016/j.ctrv.2006.05.005. Epub 2006 Jul 24.
Kempf-Bielack B, Bielack SS, Jurgens H, Branscheid D, Berdel WE, Exner GU, Gobel U, Helmke K, Jundt G, Kabisch H, Kevric M, Klingebiel T, Kotz R, Maas R, Schwarz R, Semik M, Treuner J, Zoubek A, Winkler K. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005 Jan 20;23(3):559-68. doi: 10.1200/JCO.2005.04.063.
Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, Kevric M, Jundt G, Kuhne T, Maas R, Schwarz R, Zoubek A, Jurgens H. Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 consecutive cooperative osteosarcoma study group patients. J Clin Oncol. 2009 Feb 1;27(4):557-65. doi: 10.1200/JCO.2008.16.2305. Epub 2008 Dec 15.
Leavey PJ, Mascarenhas L, Marina N, Chen Z, Krailo M, Miser J, Brown K, Tarbell N, Bernstein ML, Granowetter L, Gebhardt M, Grier HE; Children's Oncology Group. Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multi-modality therapy: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Sep;51(3):334-8. doi: 10.1002/pbc.21618.
Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS, Evans HL. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer. 2003 May 15;97(10):2530-43. doi: 10.1002/cncr.11365.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
TUVAC1
Identifier Type: -
Identifier Source: org_study_id