Safety of Peptide Vaccination for Patients With Myelodysplastic Syndrome
Condition: Myelodysplastic Syndrome (MDS)
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test whether certain patients with myelodysplastic syndrome (MDS), acute
      myeloid leukemia (AML) or chronic myeloid leukemia (CML) can safely be vaccinated with two
      peptide vaccines derived from proteins called proteinase 3 (PR1) and Wilm's tumor-1 (WT1).
      These proteins are produced in large amounts by cells of MDS, AML and CML patients. The
      peptides are combined with an "adjuvant" called Montanide to make the vaccines, and the
      vaccines are given with GM-CSF (sargramostim). Both Montanide and sargramostim help the
      immune system respond to the vaccines. The vaccines then activate the immune system to make
      specialized cells that search out and kill the MDS, AML and CML cells containing the two
      proteins.

      Patients with MDS, AML or CML who are 18 years of age or older may be eligible for this
      study. Candidates are screened with a medical history and physical examination, blood tests,
      chest x-ray, and bone marrow aspirate and biopsy. For the bone marrow biopsy, the area of the
      hip is anesthetized and a special needle is used to draw marrow from the hipbone.

      Participants receive an injection (shot) of each peptide vaccine into deep tissue of the
      upper arm, upper leg, or the abdomen and two separate shots of sargramostim in the same area
      as the vaccine shots. Patients' vital signs (heart rate, breathing rate, temperature, blood
      pressure) are measured before and after they receive the vaccines and they are watched for 2
      hours after the shots for possible side effects, such as chills, pain at the injection site,
      stomach upset, allergic reaction, low blood counts, and infection.

      Patients return to the clinic 1, 2, 3 and 4 weeks after receiving the vaccines for a brief
      physical evaluation and blood tests. A chest x-ray is also done at the 4-week visit. Patients
      may receive whole blood or platelet transfusions if needed to treat the MDS, growth factors
      (filgrastim, erythropoietin, or others) if needed, and medications to treat any infections
      that may develop.
    

Detailed description: 
      Myeloid malignancies including acute myeloid leukemia and the related disorders
      myelodysplastic syndrome (MDS) 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, a proportion of patients progress following chemotherapy
      and some relapse after transplantation. Therefore, there is need for studies of
      investigational agents to improve management of these patients.

      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+ 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.

      Therefore, we propose to evaluate a vaccine composed of peptides derived from two proteins
      over-expressed in MDS and leukemia stem cells - proteinase 3 (PR1) and Wilms tumor-1 (WT1).
      This protocol, the first in a series of planned research, will evaluate the safety of a
      single dose of a combination of two peptide vaccines, namely PR1:169-177 and WT-1:126-134 in
      Montanide adjuvant administered concomitantly with GM-CSF (Sargramostim) in select subjects
      diagnosed with MDS, AML and CML.
    

Intervention name(s): WT1 and PR1 Peptide Vaccine
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myelodyplastic Syndrome (MDS); Wilm's tumor-1; Proteinase-3; Vaccine Therapy; Acute Myeloid Leukemia; Chronic Myeloid Leukemias; Myelodysplastic Syndrome; MDS