WTI Peptide Vaccination for Patients With High Risk Hematological Malignancies
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
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell
transplantation suggests that stimulating the patient's own T cell responses to
hematological malignancies might also retard disease progression and even achieve disease
remissions. WT1 was identified as a target vaccine antigen because this antigen is
over-expressed by CD34 plus stem cells of most patients with myeloid and lymphoid
malignancies but not by normal marrow cells. An HLA-A0201 restricted peptide derived from
the WT protein is anticipated to induce T cell response against MDS and leukemic cells while
sparing normal cells. Of note, about 40% of the population is HLA-A0201 positive.
Therefore we propose this Phase II trial, the second in a series of planned peptide vaccine
research, which will evaluate the safety associated with an immunotherapy approach of
lymphodepletion, lymphocyte infusion, and WT1 vaccination in select patients diagnosed with
MDS, AML, ALL and CML. The WT1 vaccination will comprise of 9 doses of WT-1 peptide
vaccines (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim).
The primary objectives will be to evaluate the efficacy and toxicity associated with the
immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in
selected patients with hematological malignancies.
Secondary objectives will include evaluation of disease response by following the numbers of
WT1 expressing cells in blood, hematological measurements (reduction in marrow blast cells,
changes in blood counts), transfusion dependence, and time to disease progression and
The primary endpoint will be the side effects of treatment (toxicity and number of
circulating WT1 specific T cells (efficacy ) measured through week 16 of the study (7 weeks
after the last dose of vaccine).
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary objectives will to evaluate the efficacy and toxicity associated with the immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in selected patients with hematological malignancies.
12 weeks after last dose of vaccine
United States: Federal Government
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