Ignite Creation Date:
2024-05-06 @ 7:51 PM
Last Modification Date:
2024-10-26 @ 3:15 PM
Study NCT ID:
NCT06152367
Status:
COMPLETED
Last Update Posted:
2023-11-30
First Post:
2023-09-27
Brief Title:
Immunization With Autologous Dendritic Cells and Tumor Lysates in Melanoma Patients
Sponsor:
University of Chile
Organization:
University of Chile
Study Overview
Official Title:
Phase III Trial In Stage IIIIV Malignant Melanoma Using Autologous Dendritic Cells Loaded With Tumor Cell Lysates And Low Doses Of Proleukin
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Implementing this protocol has its ethical justification in that patients with metastatic melanoma once tumor invasion has reached beyond the lymph node barrier cannot possibly be treated satisfactorily with traditional surgery methods radiotherapy or conventional available chemotherapy The disseminated tumor is refractory to all standard treatments Almost 100 of patients who develop distant metastases will die from their disease either from complications or cachexia Therefore immunotherapy based on immunological stimulation with immunocompetent dendritic cells added to immunological reinforcement with IL-2 can according to the evidence emanating from ongoing clinical protocols produce a prolongation of survival with better quality and in some cases with partial or total regression of the tumor
General objective It is to study the clinical and immunological response of patients treated with vaccines based on autologous dendritic cells loaded with tumor antigens derived from allogeneic melanoma extracts in combination or not with intercalated low doses of recombinant human interleukin 2 rhIL2 PROLEUKIN aldesleukin MAIN SPECIFIC OBJECTIVE - SAFETY Safety in administering dendritic cell preparation local and systemic toxicity estimation Determination of adverse reactions such as fever nausea allergy neurological and cardiovascular symptoms Local toxicity in the administration area - MEASUREMENT OF THE IMMUNE RESPONSE Based on in vivo and in vitro parameters - In vivo response Measure the type IV Delayed Hypersensitivity DTH response It consists of a crossover test in which the response is compared to tissue interaction in vivo between dendritic cells sensitized with tumor extracts and their respective control unloaded dendritic cells - In vitro response ELISPOT assays measurement of IFN-γ gamma production in peripheral blood of treated patients Compare the specific immune response after each cycle of therapy through measurement of IFN-γ production by tumor-specific CTL Cytotoxic radioactive chromium release assays to measure anti-tumor response mediated by CTL and NK ELISA assays for quantifying cytokines IFN-γ IL-10 in patient serum after each cycle of therapy
General objective It is to study the clinical and immunological response of patients treated with vaccines based on autologous dendritic cells loaded with tumor antigens derived from allogeneic melanoma extracts in combination or not with intercalated low doses of recombinant human interleukin 2 rhIL2 PROLEUKIN aldesleukin MAIN SPECIFIC OBJECTIVE - SAFETY Safety in administering dendritic cell preparation local and systemic toxicity estimation Determination of adverse reactions such as fever nausea allergy neurological and cardiovascular symptoms Local toxicity in the administration area - MEASUREMENT OF THE IMMUNE RESPONSE Based on in vivo and in vitro parameters - In vivo response Measure the type IV Delayed Hypersensitivity DTH response It consists of a crossover test in which the response is compared to tissue interaction in vivo between dendritic cells sensitized with tumor extracts and their respective control unloaded dendritic cells - In vitro response ELISPOT assays measurement of IFN-γ gamma production in peripheral blood of treated patients Compare the specific immune response after each cycle of therapy through measurement of IFN-γ production by tumor-specific CTL Cytotoxic radioactive chromium release assays to measure anti-tumor response mediated by CTL and NK ELISA assays for quantifying cytokines IFN-γ IL-10 in patient serum after each cycle of therapy
Detailed Description:
Vaccination of Melanoma Patients Using DCs Loaded with Allogeneic Melanoma Extracts
In Chile this study constitutes the first phase I clinical trial for treating advanced malignant melanoma using dendritic cell vaccines loaded with allogeneic tumor extracts complemented or not with low doses of rIL-2 Since chemotherapy and radiotherapy only offer palliative effects in advanced melanoma resulting in an inferior prognosis for these patients the trial intends to develop a protocol that would adapt to the reality of Chile allowing for a combination of high technology and low costs
After obtaining approval from the human research ethics committee from Universidad de Chile 86 patients will be recruited who will be duly informed about the scope of these protocols and the realistic prospects of success The participants then will undergo a comprehensive health check to assess their overall health The participants will undergo a leukapheresis at the blood bank of the Clinical Hospital of the University de Chile Peripheral blood mononuclear cells PBMCs will be separated using a Ficoll-Hypaque gradient in the laboratory of Antitumor Immunology at the Institute of Biomedical Sciences Faculty of Medicine of the University de Chile Some of the cells will be cryopreserved in liquid nitrogen for future use Approximately 18x108 PBMCs will be placed in 6-well culture plates and incubated at 37C and 7 CO2 for two hours The suspended cells peripheral blood lymphocytes PBLs will be removed and frozen for later use The monocytes adhering to the plastic will be incubated for seven days in a serum-free culture medium AIM-V therapeutic GIBCO BRL in the presence of 500 Uml of IL-4 and 800 Uml of GM-CSF On the sixth day the DCs will be pulsed with tumor extracts from allogeneic melanoma cell lines previously checked for sterility and incubated for 6 hours at 37C and 7 CO2 followed by maturation stimulus with TNF-alpha for 12 to 18 hours Mature DCs will be characterized by flow cytometry Approximately 10 to 20 x 106 pulsed DCs will be subcutaneously injected This routine will be repeated weekly for at least four times and a maximum of 6 times After the fourth dose the participants general condition possible clinical regressions adverse side effects and the effects of the treatment on the immune system will be evaluated This evaluation will be done through in vivo delayed-type hypersensitivity DTH assays using melanoma extracts and their respective controls Planned in vitro assays for immune response measuring will include the detection of anti-melanoma CTL precursors by ELISPOT cytokine production proliferation assays and quantifying the CD4CD8 ratio by flow cytometry
In Chile this study constitutes the first phase I clinical trial for treating advanced malignant melanoma using dendritic cell vaccines loaded with allogeneic tumor extracts complemented or not with low doses of rIL-2 Since chemotherapy and radiotherapy only offer palliative effects in advanced melanoma resulting in an inferior prognosis for these patients the trial intends to develop a protocol that would adapt to the reality of Chile allowing for a combination of high technology and low costs
After obtaining approval from the human research ethics committee from Universidad de Chile 86 patients will be recruited who will be duly informed about the scope of these protocols and the realistic prospects of success The participants then will undergo a comprehensive health check to assess their overall health The participants will undergo a leukapheresis at the blood bank of the Clinical Hospital of the University de Chile Peripheral blood mononuclear cells PBMCs will be separated using a Ficoll-Hypaque gradient in the laboratory of Antitumor Immunology at the Institute of Biomedical Sciences Faculty of Medicine of the University de Chile Some of the cells will be cryopreserved in liquid nitrogen for future use Approximately 18x108 PBMCs will be placed in 6-well culture plates and incubated at 37C and 7 CO2 for two hours The suspended cells peripheral blood lymphocytes PBLs will be removed and frozen for later use The monocytes adhering to the plastic will be incubated for seven days in a serum-free culture medium AIM-V therapeutic GIBCO BRL in the presence of 500 Uml of IL-4 and 800 Uml of GM-CSF On the sixth day the DCs will be pulsed with tumor extracts from allogeneic melanoma cell lines previously checked for sterility and incubated for 6 hours at 37C and 7 CO2 followed by maturation stimulus with TNF-alpha for 12 to 18 hours Mature DCs will be characterized by flow cytometry Approximately 10 to 20 x 106 pulsed DCs will be subcutaneously injected This routine will be repeated weekly for at least four times and a maximum of 6 times After the fourth dose the participants general condition possible clinical regressions adverse side effects and the effects of the treatment on the immune system will be evaluated This evaluation will be done through in vivo delayed-type hypersensitivity DTH assays using melanoma extracts and their respective controls Planned in vitro assays for immune response measuring will include the detection of anti-melanoma CTL precursors by ELISPOT cytokine production proliferation assays and quantifying the CD4CD8 ratio by flow cytometry
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None