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Efficacy of WT1 and PRI Peptide Vaccination for Patients With Low Risk Myeloid Malignancies

Phase 2
18 Years
85 Years
Not Enrolling
Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML)

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Trial Information

Efficacy of WT1 and PRI Peptide Vaccination for Patients With Low Risk Myeloid 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 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.

Inclusion Criteria


Diagnosed with MDS (B subtypes RA, RARS -Low Risk) (MDS with 5q- must have failed
lenalidomide or been ineligible to receive it)


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


Diagnosed with CML in chronic phase

Unsuitable for stem cell transplantation (age over sixty or unavailability of a
fully-matched donor)


made an informed decision not to undergo the transplant procedure


are between 6 months 3 years following allogeneic SCT and fulfill the following criteria:

100% donor engraftment,

Less than 5% blasts in marrow

normal marrow cellularity

HLA-A020 1 positive at one allele

Ages 18-85 years old

Off all lymphoablative chemotherapeutic agents


- Hypoplastic MDS

- Relapsed AML

- CML in accelerated phase or blast crisis

- Hypocellular bone marrow (less than 20%)

- 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 or immunosuppresants within 14 days prior to
study entry

- Comorbidity of such severity that it would preclude the patient's ability to tolerate
protocol therapy

- Predicted survival less than 28 days

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

- Unwilling to practice abstinence or effective contraception (men and women) during
the study period.

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

June 2007

Completion Date:

April 2010

Related Keywords:

  • Myelodysplastic Syndrome (MDS)
  • Acute Myeloid Leukemia (AML)
  • Chronic Myeloid Leukemia (CML)
  • Myelodyplastic Syndrome (MDS)
  • Acute Myeloid Leukemia (AML)
  • Chronic Myeloid Leukemia (CML)
  • Wilm's Tumor-1
  • Proteinase-3
  • Myelodysplastic Syndrome
  • MDS
  • Acute Myeloid Leukemia
  • AML
  • Chronic Myeloid Leukemia
  • CML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia



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