Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00203879
Status:
COMPLETED
Last Update Posted:
2013-09-05
First Post:
2005-09-12
Brief Title:
Study of MAGE-3Melan-Agp 100NA17 and rhIL-12 WithOut Low Dose IL-2 in Metastatic Melanoma
Sponsor:
University of Chicago
Organization:
University of Chicago
Study Overview
Official Title:
Randomized Phase II Study of Immunization With MAGE-3Melan-Agp 100NA17 Peptide-Pulsed Autologous PBMC and rhIL-12 With or Without Low Dose IL-2 Inpatients With Metastatic Melanoma
Status:
COMPLETED
Status Verified Date:
2013-09
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:
Purpose of investigation Primary hypotheses Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8 T cells against all 4 antigens simultaneously Immunization with 4 melanoma antigen peptides will increase the response rate from 10 to 30 Administration of low-dose IL-2 following each vaccine will result in a greater than 3-fold increase in specific T cells compared to no IL-2
Secondary hypotheses Immunization will clear the blood of detectable circulating melanoma cells Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens class I MHC or the TAP peptide transporter or may fail to show increased expression of mRNA for IFN-y or perforin Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination
Secondary hypotheses Immunization will clear the blood of detectable circulating melanoma cells Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens class I MHC or the TAP peptide transporter or may fail to show increased expression of mRNA for IFN-y or perforin Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination
Detailed Description:
Based on the above preclinical and Phase I results a logical strategy for a second generation melanoma vaccine has emerged A randomized Phase II study in metastatic melanoma patients will be undertaken Patients first will be HLA-typed HLA-A2-positive patients will be eligible for screening When feasible each patient will undergo a tumor biopsy to screen for expression of MAGE-3 Melan-A gplOO and NAI 7 using RT-PCR and immunohistochemistry to determine whether T cells are present in the lesion to measure cytokine gene expression by RT-PCR and to perform gene array analysis In addition blood cells will be analyzed for certain parameters of T cell function
Patients will be randomized to cohorts A no IL-2 or B with low-dose IL-2 For treatment peripheral blood will be collected and fractionated by density centrifugation to isolate PBMC as a source of APC The PBMC will be divided into four pools each of which will be incubated with one of the following peptides MAGE-3 Melan-A gp 100 or Ni 7A The peptide-loaded cells will then be washed and recombined into a single suspension in PBS and lethally irradiated Approximately 120 x 106 pulsed cells will be injected subcutaneously at a site near a lymph node not thought to be involved with tumor The subcutaneous route has been selected for the reasons of safety efficacy in the preclinical model and the goal of targeting the vaccine to a draining lymph node rhIL-12 4 tg straight dose will then be given subcutaneously adjacent to the vaccine site days 13 and 5 of each cycle This dose and schedule was found to be effective in our phase I study In one-half of the patients cohort B IL-2 I MU straight dose will be administered subcutaneously daily days 7-18 Re-immunization along with rhIL-12 followed by IL-2 if assigned will be performed at 3 week intervals as in cycle I
On day 1 of each cycle peripheral blood will be collected to measure peptide-specific IFN-y production Before treatment and after every 3 cycles PBMC will be collected to quantify peptide specific CD8 T cells by flow cytometric analysis with peptideHLA-A2 tetramers and evidence for a molecular response will be assessed by performing RT-PCR for melanoma antigens on peripheral blood samples In addition prior to treatment after the first 3 cycles and at the time of going off- study a tumor biopsy will be performed to assess the immune response in the tumor microenvironment including gene array analysis It is hoped that these studies will uncover the reason for lack of clinical response in patients with residual tumors Clinical response will be assessed as a secondary outcome
Patients will be randomized to cohorts A no IL-2 or B with low-dose IL-2 For treatment peripheral blood will be collected and fractionated by density centrifugation to isolate PBMC as a source of APC The PBMC will be divided into four pools each of which will be incubated with one of the following peptides MAGE-3 Melan-A gp 100 or Ni 7A The peptide-loaded cells will then be washed and recombined into a single suspension in PBS and lethally irradiated Approximately 120 x 106 pulsed cells will be injected subcutaneously at a site near a lymph node not thought to be involved with tumor The subcutaneous route has been selected for the reasons of safety efficacy in the preclinical model and the goal of targeting the vaccine to a draining lymph node rhIL-12 4 tg straight dose will then be given subcutaneously adjacent to the vaccine site days 13 and 5 of each cycle This dose and schedule was found to be effective in our phase I study In one-half of the patients cohort B IL-2 I MU straight dose will be administered subcutaneously daily days 7-18 Re-immunization along with rhIL-12 followed by IL-2 if assigned will be performed at 3 week intervals as in cycle I
On day 1 of each cycle peripheral blood will be collected to measure peptide-specific IFN-y production Before treatment and after every 3 cycles PBMC will be collected to quantify peptide specific CD8 T cells by flow cytometric analysis with peptideHLA-A2 tetramers and evidence for a molecular response will be assessed by performing RT-PCR for melanoma antigens on peripheral blood samples In addition prior to treatment after the first 3 cycles and at the time of going off- study a tumor biopsy will be performed to assess the immune response in the tumor microenvironment including gene array analysis It is hoped that these studies will uncover the reason for lack of clinical response in patients with residual tumors Clinical response will be assessed as a secondary outcome
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