Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00027144
Status:
COMPLETED
Last Update Posted:
2005-06-24
First Post:
2001-11-27
Brief Title:
Study Using Vaccination With Heat Shock Protein 70 HSP70 for the Treatment of CML in Chronic Phase
Sponsor:
University of Connecticut
Organization:
UConn Health
Study Overview
Official Title:
A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase
Status:
COMPLETED
Status Verified Date:
2001-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Description The trial is designed to determine the response of the immune system of patients with CML to a vaccine made from their own tumor Researchers believe that this particular vaccine which is made from purified heat shock proteins taken from each patients tumor alerts the bodys immune system to recognize and attack invading cancer To be considered potentially eligible for this study you must have CML in the chronic phase
LengthDuration Vaccinations will be administered weekly for eight weeks One clinic follow up visit will be scheduled two weeks after the final vaccination
LengthDuration Vaccinations will be administered weekly for eight weeks One clinic follow up visit will be scheduled two weeks after the final vaccination
Detailed Description:
Rational for immunotherapy of CML
ConceptuallyCML in chronic phase is the best model for immunological intervention It is a disease as a result of chromosomal translocation which generates a true tumor-specific antigen Patients in chronic phase have relatively preserved immune function for a prolonged period of time Studies have indeed shown that peptides spanning the junctional region of both the bcrabl and ablbcr fusion proteins can bind to major histocompatibility complex MHC class I molecules Berke et al 2000 Vaccination of patients with bcrabl breakpoint fusion peptides generates specific immune responses Pinilla-Ibarz et al 2000 In addition for patients relapsed after bone marrow or stem cell transplant donor lymphocyte infusion is effective in inducing a majority of them into remission The role of donor lymphocyte infusion has proven the original concept of graft versus leukemia effect and the effectiveness of immunotherapy in practice towards CML Dazzi et al 1999 More recently it was found that the presence of cytotoxic T lymphocytes CTL against HLA-A2-restricted myeloid-specific antigen proteinase 3 correlates significantly with cytogenetic remission of CML treated either with IFN or stem cell transplant Molldrem et al 2000 which provides strong evidence for a role of T cell immunity in clearing malignant cells
Current proposal and hypothesis
Based on the established roles of HSPs in T cell immunity and a large body of preclinical and clinical safety data we propose to initiate a pilot study to test the feasibility of immunization with autologous tumor-derived HSP70 in the treatment of CML in chronic phase This study will facilitate more clinical trials in the future testing the ultimate hypothesis that the combination of the cytostatic therapy such as IFN and STI571 with specific immunomodulator such as HSP70 offers the best chance of eradication of CML A total of 10 eligible patients will be enrolled in the study All eligible patients will undergo aphaeresis to collect peripheral blood mononuclear cells The autologous HSP70 is then purified using the standard protocol After passing the established sterility testing the patients are immunized intradermally with 50 micrograms HSP70 for a total of 8 injections in 2 months They may receive their standard therapy during this time In addition to collecting the feasibility and toxicity data the development of anti-tumor immunity will be measured by
1 an increase in peripheral blood of IFN-gamma producing CD8 T-lymphocytes which are reactive to the autologous bcrabl positive peripheral mononuclear cells
2 an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are HLA-A2 positive
3 the change of immunophenotype of peripheral lymphocytes
4 the cytogenetic remission of Philadelphia chromosome from the bone marrow
ConceptuallyCML in chronic phase is the best model for immunological intervention It is a disease as a result of chromosomal translocation which generates a true tumor-specific antigen Patients in chronic phase have relatively preserved immune function for a prolonged period of time Studies have indeed shown that peptides spanning the junctional region of both the bcrabl and ablbcr fusion proteins can bind to major histocompatibility complex MHC class I molecules Berke et al 2000 Vaccination of patients with bcrabl breakpoint fusion peptides generates specific immune responses Pinilla-Ibarz et al 2000 In addition for patients relapsed after bone marrow or stem cell transplant donor lymphocyte infusion is effective in inducing a majority of them into remission The role of donor lymphocyte infusion has proven the original concept of graft versus leukemia effect and the effectiveness of immunotherapy in practice towards CML Dazzi et al 1999 More recently it was found that the presence of cytotoxic T lymphocytes CTL against HLA-A2-restricted myeloid-specific antigen proteinase 3 correlates significantly with cytogenetic remission of CML treated either with IFN or stem cell transplant Molldrem et al 2000 which provides strong evidence for a role of T cell immunity in clearing malignant cells
Current proposal and hypothesis
Based on the established roles of HSPs in T cell immunity and a large body of preclinical and clinical safety data we propose to initiate a pilot study to test the feasibility of immunization with autologous tumor-derived HSP70 in the treatment of CML in chronic phase This study will facilitate more clinical trials in the future testing the ultimate hypothesis that the combination of the cytostatic therapy such as IFN and STI571 with specific immunomodulator such as HSP70 offers the best chance of eradication of CML A total of 10 eligible patients will be enrolled in the study All eligible patients will undergo aphaeresis to collect peripheral blood mononuclear cells The autologous HSP70 is then purified using the standard protocol After passing the established sterility testing the patients are immunized intradermally with 50 micrograms HSP70 for a total of 8 injections in 2 months They may receive their standard therapy during this time In addition to collecting the feasibility and toxicity data the development of anti-tumor immunity will be measured by
1 an increase in peripheral blood of IFN-gamma producing CD8 T-lymphocytes which are reactive to the autologous bcrabl positive peripheral mononuclear cells
2 an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are HLA-A2 positive
3 the change of immunophenotype of peripheral lymphocytes
4 the cytogenetic remission of Philadelphia chromosome from the bone marrow
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None