Ignite Creation Date:
2024-05-05 @ 5:35 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00488592
Status:
COMPLETED
Last Update Posted:
2021-07-12
First Post:
2007-06-19
Brief Title:
Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Efficacy of Peptide WT1 and PeptidePRI Vaccination for Patients With Low Risk Myeloid Malignancies
Status:
COMPLETED
Status Verified Date:
2014-06
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:
This study will test the safety and effectiveness of two vaccines on slowing disease progression improving blood counts reducing the need for transfusions of blood and platelets or achieving remission in patients with myelodysplastic syndrome MDS also known as myelodysplasia acute myeloid leukemia AML or chronic myeloid leukemia CML The vaccines consist of peptides parts of proteins found in MDS AML and CML stem cells combined with a substance called MontanideTM They are administered with granulocyte- macrophage colony- stimulating factor GM-CSF The Montanide and the GM-CSF help the immune system respond to the vaccines
People 18 years of age or older with MDS AML or CML may be eligible for this study
Participants receive six injections of the vaccines one dose every other week for a total of 10 weeks The injections are given in the upper arm upper leg or abdomen A separate injection of GM-CSF is given in the same area as the vaccine injections Subjects are observed for 2 hours after the first vaccination and at least 30 minutes after each subsequent vaccination for allergic reactions In addition to the vaccination subjects undergo the following
History and physical exam chest x-ray blood tests and bone marrow aspirate and biopsy before starting the vaccinations
Safety monitoring during vaccine administration every other week for 10 weeks with blood tests and check of vital signs
Follow-up safety monitoring weeks 12 and 16 with blood tests every visit chest x-ray at week 12 and bone marrow biopsy visit 16
People 18 years of age or older with MDS AML or CML may be eligible for this study
Participants receive six injections of the vaccines one dose every other week for a total of 10 weeks The injections are given in the upper arm upper leg or abdomen A separate injection of GM-CSF is given in the same area as the vaccine injections Subjects are observed for 2 hours after the first vaccination and at least 30 minutes after each subsequent vaccination for allergic reactions In addition to the vaccination subjects undergo the following
History and physical exam chest x-ray blood tests and bone marrow aspirate and biopsy before starting the vaccinations
Safety monitoring during vaccine administration every other week for 10 weeks with blood tests and check of vital signs
Follow-up safety monitoring weeks 12 and 16 with blood tests every visit chest x-ray at week 12 and bone marrow biopsy visit 16
Detailed Description:
Leukemias and the related disorders myelodysplastic syndrome and myeloproliferative diseases represent a wide group of bone marrow stem cell malignancies Some patients can be cured with chemotherapy or by allogeneic stem cell transplantation However standard treatment approaches are not effective for patients who become refractory to chemotherapy those who relapse after transplantation and those with progressive disease The management of such patients remains unsatisfactory and requires new treatment approaches other than chemotherapy
The immunological graft-versus-leukemia GVL effect seen after allogeneic stem cell transplantation suggests that stimulating the patients own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions Peptide WT1 and peptide PR1 were identified as target antigens because both antigens are highly expressed by cluster of differentiation 34 CD34 plus stem cells of most patients with myeloid malignancies but not by normal marrow cells An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could induce T cell response against MDS and leukemic cells while sparing normal cells and by using a combination of two antigens the risk of disease escape by antigen down regulation should be further diminished Indeed in a safety study of one dose of a combination of peptide PRl and WT1 vaccination we demonstrated that immunological response against one or both vaccines could be induced in all subjects who were vaccinated This immunological response was associated with a transient reduction in the leukemia burden Furthermore the vaccine combination was well tolerated
Therefore we propose this Phase II trial the third in a series of planned peptide vaccine research protocols which will evaluate the safety and efficacy associated with an immunotherapy approach using two peptide vaccines namely PR 1 169- 177 and WT-1 126-1 34 in Montanide adjuvant administered concomitantly with GM-CSF Sargramostim every 2 weeks for 10 weeks 6 doses WT1 plus 6 doses PRl plus GM-CSF in select patients diagnosed with MDS AML or CML Subjects with immunological response to one or both peptide vaccines will have the option of receiving an additional 6 boosters of the WT-1126-135 and PR1169-177 peptide vaccines at 3 monthly intervals
The primary objective will be to evaluate the efficacy and toxicity associated with 6 doses of a combination of WT-1 126-134 and PRl 169-177 peptide vaccines in Montanide adjuvant administered concomitantly with GMCSF Sargramostim in selected patients with myeloid malignancies MDS AML CML
The primary endpoint will be immune response studying changes in the frequencies of circulating PR1 and WT1 specific T cells which will serves as a surrogate for evaluating for the efficacy of the study
Secondary Endpoints will include changes in marrow blast cells blood counts transfusion dependence time to disease progression and survival
The immunological graft-versus-leukemia GVL effect seen after allogeneic stem cell transplantation suggests that stimulating the patients own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions Peptide WT1 and peptide PR1 were identified as target antigens because both antigens are highly expressed by cluster of differentiation 34 CD34 plus stem cells of most patients with myeloid malignancies but not by normal marrow cells An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could induce T cell response against MDS and leukemic cells while sparing normal cells and by using a combination of two antigens the risk of disease escape by antigen down regulation should be further diminished Indeed in a safety study of one dose of a combination of peptide PRl and WT1 vaccination we demonstrated that immunological response against one or both vaccines could be induced in all subjects who were vaccinated This immunological response was associated with a transient reduction in the leukemia burden Furthermore the vaccine combination was well tolerated
Therefore we propose this Phase II trial the third in a series of planned peptide vaccine research protocols which will evaluate the safety and efficacy associated with an immunotherapy approach using two peptide vaccines namely PR 1 169- 177 and WT-1 126-1 34 in Montanide adjuvant administered concomitantly with GM-CSF Sargramostim every 2 weeks for 10 weeks 6 doses WT1 plus 6 doses PRl plus GM-CSF in select patients diagnosed with MDS AML or CML Subjects with immunological response to one or both peptide vaccines will have the option of receiving an additional 6 boosters of the WT-1126-135 and PR1169-177 peptide vaccines at 3 monthly intervals
The primary objective will be to evaluate the efficacy and toxicity associated with 6 doses of a combination of WT-1 126-134 and PRl 169-177 peptide vaccines in Montanide adjuvant administered concomitantly with GMCSF Sargramostim in selected patients with myeloid malignancies MDS AML CML
The primary endpoint will be immune response studying changes in the frequencies of circulating PR1 and WT1 specific T cells which will serves as a surrogate for evaluating for the efficacy of the study
Secondary Endpoints will include changes in marrow blast cells blood counts transfusion dependence time to disease progression and survival
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-H-0159 | OTHER | National Heart Lung and Blood Institute | None |