Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
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 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.
Myelodysplastic Syndrome (MDS)
Acute Myeloid Leukemia (AML)
Chronic Myeloid Leukemia (CML)
Biological: WT1:126-134 Peptide
Biological: PR1:169-177 Peptide
Drug: WT1 and PR1 Peptide Vaccines
Drug: GM-CSF (Sargramostim)
Biological: WT1 and PR1 Peptide Vaccines
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy of WT1 and PRI Peptide Vaccination for Patients With Low Risk Myeloid Malignancies|
- The efficacy and toxicity associated with 6 doses of a combination of WT-1:126-134 and PR1:169-177 peptide vaccines in selected patients with myeloid malignancies. [ Designated as safety issue: Yes ]
- Changes in marrow blast cells, blood counts, transfusion dependence, time to disease progression, survival and response to booster vaccination. [ Designated as safety issue: Yes ]
|Study Start Date:||June 2007|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Biological: WT1:126-134 Peptide
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 patient's own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions. WT1 and PR1 were identified as target antigens because both antigens are highly expressed by 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 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-1:126-135 and PR1:169-177 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.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|