Ignite Creation Date:
2024-05-05 @ 9:37 PM
Last Modification Date:
2024-10-26 @ 10:07 AM
Study NCT ID:
NCT00923910
Status:
COMPLETED
Last Update Posted:
2017-04-12
First Post:
2009-06-17
Brief Title:
Wilms Tumor 1 Protein Vaccine to Treat Cancers of the Blood
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies
Status:
COMPLETED
Status Verified Date:
2017-03
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:
Background
Most patients with acute lymphoblastic leukemia ALL and many patients with acute myelogenous leukemia AML chronic myelogenous leukemia CML and non-Hodgkins lymphoma NHL have a protein called Wilms Tumor 1 WT1 in their cancer cells This protein is thought to be able to influence the growth of these cancers
A vaccine made with the WT1 protein may boost the immune system to help fight these cancers in patients whose cancer cells contain the protein
Objectives
To determine the safety effectiveness and side effects of giving the WT1 vaccine and donor white blood cells to patients with AML ALL CML or NHL who have previously received standard treatment and undergone stem cell transplantation
To determine the immune response to the WT1 vaccine and donor white blood cells in these patients and to determine if the response is related to the amount of WT1 protein in the patients cancer cells
Eligibility
Patients between 1 and 75 years of age with the blood antigen human leukocyte antigen HLA-A2 and the WT1 cancer protein who have persistent or recurrent blood cancers after stem cell transplantation
The prior stem cell transplant donor must be willing to provide additional cells which will be used to prepare the cellular vaccines and for donor lymphocyte white blood cell infusions
Design
Patients are given the WT1 vaccine every 2 weeks for 6 weeks weeks 0 2 4 6 8 10 Each vaccination consists of two injections in the upper arm or thigh
On weeks 0 4 and 8 patients also receive white blood cells from a donor to enhance the immune response The cells are also given as a 15- to 30-minute infusion through a vein about 1 hour after the vaccine injection Donor infusions are given only to patients with mild or no graft-vs-host disease resulting from their prior stem cell transplantation
Periodic physical examinations blood and urine tests scans to evaluate disease and other tests as needed are done for 12 months after enrollment in the study
Most patients with acute lymphoblastic leukemia ALL and many patients with acute myelogenous leukemia AML chronic myelogenous leukemia CML and non-Hodgkins lymphoma NHL have a protein called Wilms Tumor 1 WT1 in their cancer cells This protein is thought to be able to influence the growth of these cancers
A vaccine made with the WT1 protein may boost the immune system to help fight these cancers in patients whose cancer cells contain the protein
Objectives
To determine the safety effectiveness and side effects of giving the WT1 vaccine and donor white blood cells to patients with AML ALL CML or NHL who have previously received standard treatment and undergone stem cell transplantation
To determine the immune response to the WT1 vaccine and donor white blood cells in these patients and to determine if the response is related to the amount of WT1 protein in the patients cancer cells
Eligibility
Patients between 1 and 75 years of age with the blood antigen human leukocyte antigen HLA-A2 and the WT1 cancer protein who have persistent or recurrent blood cancers after stem cell transplantation
The prior stem cell transplant donor must be willing to provide additional cells which will be used to prepare the cellular vaccines and for donor lymphocyte white blood cell infusions
Design
Patients are given the WT1 vaccine every 2 weeks for 6 weeks weeks 0 2 4 6 8 10 Each vaccination consists of two injections in the upper arm or thigh
On weeks 0 4 and 8 patients also receive white blood cells from a donor to enhance the immune response The cells are also given as a 15- to 30-minute infusion through a vein about 1 hour after the vaccine injection Donor infusions are given only to patients with mild or no graft-vs-host disease resulting from their prior stem cell transplantation
Periodic physical examinations blood and urine tests scans to evaluate disease and other tests as needed are done for 12 months after enrollment in the study
Detailed Description:
Background
Efforts to incorporate anti-tumor immunotherapy at stages of minimal residual disease MRD burden are limited by profound host immune depletion associated with standard anti-cancer therapies
Allogeneic blood and marrow stem cell transplantation SCT can be curative for a number of hematologic malignancies Part of the success of this approach is an allogeneic immunologic reaction that has been demonstrated to play a role in the eradication of residual malignant disease after transplant in certain cancers the so called graft-versus-leukemia GVL or graft-versus-tumor GVT effect Nonetheless relapse remains the primary cause of treatment failure after allogeneic SCT
The Wilms tumor 1 WT1 gene product is a tumor-associated antigen that represents a potential target for immunotherapy in a wide array of cancers WT1 is expressed in most cases of acute leukemia and in many cases of chronic myelogenous leukemia and myelodysplastic syndromes Importantly WT1 has limited expression in normal tissues beyond embryogenesis This trial represents an attempt to incorporate antigen-specific immunotherapy in the setting of allogeneic adoptive cell transfer
Objectives
To determine the safety toxicity and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusion DLI after allogeneic SCT
To determine the frequency and severity of graft-vs-host disease GVHD in patients treated with peptide-loaded donor-derived dendritic cell vaccination and donor lymphocyte infusion DLI
To evaluate whether immunologic responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
To evaluate whether clinical responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
To evaluate whether immunologic andor clinical responses may be associated with the degree of WT1 expression by malignant cells or pre-existing donor anti-WT1 immunity
Eligibility
HLA-A2 plus patients may be enrolled on this trial if they have relapsed or residual disease following allogeneic SCT for a WT1 expressing hematologic malignancy
Donors from the previous SCT related or unrelated must be 5- or 6- antigen genotypic HLA-matched single HLA-A or B locus mismatch allowed and HLAA2 plus
Design
This is a pilot study the primary aim of which is to assess safety and feasibility of this novel vaccine strategy aimed to enhance the GVL effect after allogeneic SCT
Donor-derived dendritic cells prepared from peripheral blood monocytes will be loaded with a combination of three WT1-derived peptides These peptides are each comprised of one WT1-derived oligomeric epitope known to bind to HLA-A2 and an 11-mer protein transduction epitope known to enhance peptide loading and antigen presentation
Patients will receive donor-derived dendritic cell vaccines every 14 days for 6 doses Donor leukocyte infusions DLI will also be administered with the vaccine
Study endpoints will include toxicity feasibility antigen-specific immunity and disease response
This is an exploratory pilot trial Up to 12 patients will be treated
Stopping rules will take effect if excessive toxicity eg GVHD or inability to generate vaccines are observed
Efforts to incorporate anti-tumor immunotherapy at stages of minimal residual disease MRD burden are limited by profound host immune depletion associated with standard anti-cancer therapies
Allogeneic blood and marrow stem cell transplantation SCT can be curative for a number of hematologic malignancies Part of the success of this approach is an allogeneic immunologic reaction that has been demonstrated to play a role in the eradication of residual malignant disease after transplant in certain cancers the so called graft-versus-leukemia GVL or graft-versus-tumor GVT effect Nonetheless relapse remains the primary cause of treatment failure after allogeneic SCT
The Wilms tumor 1 WT1 gene product is a tumor-associated antigen that represents a potential target for immunotherapy in a wide array of cancers WT1 is expressed in most cases of acute leukemia and in many cases of chronic myelogenous leukemia and myelodysplastic syndromes Importantly WT1 has limited expression in normal tissues beyond embryogenesis This trial represents an attempt to incorporate antigen-specific immunotherapy in the setting of allogeneic adoptive cell transfer
Objectives
To determine the safety toxicity and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusion DLI after allogeneic SCT
To determine the frequency and severity of graft-vs-host disease GVHD in patients treated with peptide-loaded donor-derived dendritic cell vaccination and donor lymphocyte infusion DLI
To evaluate whether immunologic responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
To evaluate whether clinical responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
To evaluate whether immunologic andor clinical responses may be associated with the degree of WT1 expression by malignant cells or pre-existing donor anti-WT1 immunity
Eligibility
HLA-A2 plus patients may be enrolled on this trial if they have relapsed or residual disease following allogeneic SCT for a WT1 expressing hematologic malignancy
Donors from the previous SCT related or unrelated must be 5- or 6- antigen genotypic HLA-matched single HLA-A or B locus mismatch allowed and HLAA2 plus
Design
This is a pilot study the primary aim of which is to assess safety and feasibility of this novel vaccine strategy aimed to enhance the GVL effect after allogeneic SCT
Donor-derived dendritic cells prepared from peripheral blood monocytes will be loaded with a combination of three WT1-derived peptides These peptides are each comprised of one WT1-derived oligomeric epitope known to bind to HLA-A2 and an 11-mer protein transduction epitope known to enhance peptide loading and antigen presentation
Patients will receive donor-derived dendritic cell vaccines every 14 days for 6 doses Donor leukocyte infusions DLI will also be administered with the vaccine
Study endpoints will include toxicity feasibility antigen-specific immunity and disease response
This is an exploratory pilot trial Up to 12 patients will be treated
Stopping rules will take effect if excessive toxicity eg GVHD or inability to generate vaccines are observed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 08-C-0051 | None | None | None |