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Safety of WT1 and PR1 Peptide Vaccination for Patients With Myeloid Malignancies


Phase 1
18 Years
85 Years
Not Enrolling
Both
Myelodysplastic Syndrome (MDS)

Thank you

Trial Information

Safety of WT1 and PR1 Peptide Vaccination for Patients With Myeloid Malignancies


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.

Inclusion Criteria


- INCLUSION CRITERIA:

Diagnosed with FAB subtypes RA, RARS MDS (Low Risk)

OR

Diagnosed with AML and in complete remission within 5 years of treatment with less than 5
percent marrow blasts

OR

Diagnosed with CML In chronic phase

OR

Diagnosed with MDS, AML or CML and are between 6 months-3 years following allogeneic SCT
who fulfill the following criteria:

100 percent donor engraftment,

less than 5 percent blasts in marrow

normal marrow cellularity

HLA-A0201 positive at one allele

Ages 18 - 85 years old

EXCLUSION CRITERIA:

Hypoplastic MDS

Relapsed AML

CML in accelerated phase or blast crisis

Relapsed MDS, AML or CML following hematopoietic stem cell transplantation

Hb less than 9 g/dl, neutrophil count less than 1 times 10(9)/1, and/ or platelet count
less than 75 times 10(9)/1

Hypocellular bone marrow

History of Wegener's granulomatosis

Serologic antibody against proteinase-3 (ANCA positive)

Previous allergic reaction to montanide adjuvant

Positive test for HIV

Treatment with systemic corticosteroids within 14 days prior to study entry

Co-morbidity of such severity that it would preclude the subject's ability to tolerate
protocol therapy

Predicted survival less than 28 days

Pregnant or breast feeding (All female subjects must have a urine pregnancy test within 1
week prior to vaccine administration)

Enrolled in another drug or vaccine clinical trial during the study period

Inability to comprehend the investigational nature of the study and provide informed
consent

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie...

Principal Investigator

Gregory J Kato, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)

Authority:

United States: Federal Government

Study ID:

060062

NCT ID:

NCT00270452

Start Date:

December 2005

Completion Date:

October 2007

Related Keywords:

  • Myelodysplastic Syndrome (MDS)
  • Myelodyplastic Syndrome (MDS)
  • Wilm's tumor-1
  • Proteinase-3
  • Vaccine Therapy
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemias
  • Myelodysplastic Syndrome
  • MDS
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892