Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Myeloid Neoplasms

Design:

This will be a pilot trial evaluating the safety and immunogenicity of the WT-1 peptide
vaccine in patients with hematologic malignancies. Ten patients with acute myelogenous
leukemia (AML) or advanced myelodysplastic syndrome (MDS), will be enrolled. Patients will
be vaccinated with a preparation of WT-1-derived native and synthetic peptides plus
immunologic adjuvant Montanide ISA 51 VG (Seppic Pharmaceuticals, Fairfield, NJ) and
Sargramostim (GM-CSF). One dose level will be tested.

Patients will receive 6 injections of the WT-1 vaccine. Doses will be given every 2 weeks.
Each vaccine is given at a different location under the skin in the arm or leg. Patients
will be monitored for 30 minutes after vaccination.

WT-1 vaccine is given with another substance, Montanide, which clumps the WT-1 vaccine and
improves the immune response. Patients will also receive an injection of Sargramostim
(GM-CSF) 2 days before each vaccination and again on the day of the WT-1 injection at the
same spot. Sargramostim (GM-CSF) stimulates the body's white blood cells to boost the immune
response. Patients may be taught to do the Sargramostim (GM-CSF) injection themselves in
which case patients will be given a log sheet to record the injection time and location. If
not, they will need to come for an additional 24 study visits.

To monitor their health while receiving the vaccine, patients will need the following tests
and procedures as a part of regular cancer care.

- History and physical examination every 2 weeks

- Complete blood count (CBC) and comprehensive panel every 2 weeks

- Bone marrow aspirate at week 14 for patients with acute myelogenous leukemia or
myelodysplastic syndrome.

Patients will need these tests and procedures to see whether the vaccine is causing an
immune response:

- A skin test will be performed before patients start the study and again in the 8th and
14th weeks in which a small amount of the vaccine will be placed under the skin. Two
days later, the site will be checked to see whether a bump or swelling has formed.
Another substance which typically does cause a mild reaction (mumps) will also be
placed under the skin to measure whether they have a normal immune reaction.

- We will take about 7 tablespoons of blood to measure their immune response. About 1
tablespoon of blood will be taken to measure the levels of WT-1 in their blood. Blood
samples will be taken prior to receiving the first vaccination and prior to receiving
the vaccination at weeks 6 and 12.

If the vaccine causes the patient to have an immune response, and their cancer does not
grow, they may continue to receive the WT-1 vaccinations monthly for 6 more months. If this
occurs, the patient will have a computed tomography (CT) scan or bone marrow test and
immunology blood tests 2 weeks after the 9th and 12th vaccinations.

Inclusion Criteria:

- Cytologic or histologic diagnosis of acute myelogenous leukemia or myelodysplastic
syndrome confirmed at Moffitt Cancer Center.

- Patients with acute myelogenous leukemia will have completed induction chemotherapy,
achieved CR1 or CR2, and will have completed any planned postremission therapy (at
discretion of treating physician),with no plan for allogenic or autologous
transplant.

- Patients with myelodysplastic syndrome who according to the IPSS scoring system are
category Int-2 or greater, with disease that relapsed, progressed, or not responded
to at least 1 prior course of approved therapy for MDS (i.e. hypomethylating agent or
lenalidomide).

- Patients with AML/MDS must have documented WT-1 + disease. For purposes of this
study, this may be either the demonstration of WT-1 protein on a pretreatment bone
marrow biopsy or detectable disease with RQ-PCR. For patients in whom a bone marrow
aspirate is not available or possible (e.g. "dry tap"), a peripheral blood sample may
be used for WT-1 screening. In such cases, 10 cc of peripheral blood will be
collected in a heparinized tube.

- At least 4 weeks must have elapsed between the patient's last chemotherapy or
radiation treatment and the first vaccination.

- Karnofsky performance status ≥ 70%

- Hematologic parameters:

- Absolute neutrophil count ≥ 1000/mcL (except for MDS, for which the parameter is
≥ 500/mcL)

- Platelets > 50 K/mcL (except for MDS for which the parameter is > 25 K/mcL and
not transfusion dependent)

- Biochemical parameters:

- Total bilirubin ≤ 2.0 mg/dl

- Aspartic transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 x upper limits
of normal

- Creatinine ≤ 2.0 mg/dl

Exclusion Criteria:

- Pregnant or lactating women

- Patients with leptomeningeal disease

- Patients with active infection requiring systemic antibiotics, antiviral, or
antifungal treatments

- Patients with serious unstable medical illness

- Patients taking systemic corticosteroids

- Patients with central nervous system (CNS) involvement with cancer/leukemia