Wilm's Tumor 1 (WT1) Peptide Vaccine for High Risk Hematologic Malignancy
Condition: Myelodysplastic Syndrome; Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Wilms Tumor; Myelodysplastic Syndromes; Syndrome
Intervention: WT1 Peptide Vaccine
Intervention description: WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Myelodysplastic Syndrome (MDS); Acute Myelogenous Leukemia (AML); Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Wilm's Tumor-1 Peptide; Leukemia; Myelodysplastic Syndrome; MDS; Acute Myelogenous Leukemia; AML; Chronic Myelogenous Leukemia; CML; Acute Lymphoblastic Leukemia; ALL

Summary:

      This study will determine the safety and effectiveness of an experimental vaccine in
      controlling the abnormal growth of cells in patients with myelodysplastic syndrome (MDS, also
      known as myelodysplasia), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL),
      and chronic myeloid leukemia (CML). It will test whether the vaccine can increase the number
      of immune cells responding to the cancer and thereby slow progression of the illness, improve
      blood counts, reduce the need for transfusions of blood and platelets, or even achieve a
      disease remission. The vaccine contains part of a protein that is produced in large amounts
      by cells of patients with these cancers and an added substance called Montanide that helps
      the immune system respond to the vaccine. Sargramostim, another substances that boosts the
      immune response, is also given.

      Patients 18 to 85 years of age with MDS, AML, ALL or CML may be eligible for this study.
      Candidates are screened with a medical history, physical examination, blood tests, chest
      x-ray and bone marrow biopsy. Women of childbearing age also have a pregnancy test.

      Participants undergo the following:

        -  Chemotherapy entering the study.

        -  Leukapheresis to collect large amounts of white blood cells for infusion before vaccine
           administration.

        -  Participants may need placement of a central line (plastic tube, or catheter) in the
           upper part of the chest to be used for giving chemotherapy, blood or platelet
           transfusions, antibiotics and white blood cells, and for collecting blood samples.

        -  Weekly vaccine injections for nine weeks, given in the upper arm, upper leg or abdomen.

        -  Sargramostim injections following each vaccination.

        -  Standard of care treatment for MDS, AML, ALL or CML, which may include blood or platelet
           transfusions, growth factors, and drugs to control underlying disease and potential side
           effects of the vaccine.

        -  Weekly safety monitoring, including vital signs check, brief health assessment, blood
           tests and observation after the vaccination, on the day of each vaccination.

        -  Follow-up evaluations with blood tests and chest x-ray 3 weeks after the last vaccine
           dose and with blood tests and bone marrow biopsy 7 weeks after the last vaccine dose.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Diagnosed with

                  refractory anemia with excess of blasts (MDS-RAEB).

                  or

                  refractory anemia with excess of blasts in transformation (MDS-RAEBt).

                  or

                  secondary acute myelogenous leukemia (AML).

                  or

                  relapsed or refractory acute or chronic myelogenous leukemias (AML).

                  or

                  relapsed or refractory chronic myelogenous leukemias (CML) with accelerated phase
                  or blast crisis

                  or

                  relapsed or refractory acute lymphoblastic leukemia (high risk ALL).

                  or

                  acute lymphoblastic leukemia (ALL) in complete remission.

                  or

                  chronic myelomonocytic leukemia (CMML).

               2. Unsuitable for stem cell transplantation (age over sixty or unavailability of a
                  fully-matched donor).

                  or

                  made an informed decision not to undergo the transplant procedure.

                  or

                  relapsed AML, CML, MDS or ALL post stem cell transplantation (SCT).

               3. HLA-A0201 positive.

               4. Ages 18 - 85 years.

               5. Off all lympho-ablative chemotherapeutic agents.

               6. All subjects (men and women) must agree to practice abstinence or effective
                  contraception during the study period.

        Inclusion Criteria Donor (for post transplant subjects without available donor lymphocyte
        infusion (DLI) cells):

          1. Related donor, HLA identical (6/6) with recipient.

          2. Age greater than or equal to 18 or less than or equal to 80 years old.

          3. Ability to comprehend the investigational nature of the study and provide informed
             consent.

        EXCLUSION CRITERIA:

          1. HIV positive (HIV-infected patients are immune-compromised and it is unlikely that
             these patients will be capable of mounting an immune response to the vaccine).

          2. Treatment with systemic corticosteroids within 7 days prior to study entry.

          3. Low bone marrow reserves (less than 20 percent cellularity).

          4. Serum creatinine greater than 2.5mg/dl or serum bilirubin greater than 4mg/dl
             (patients receiving fludarabine).

          5. Co-morbidity of such severity that it would preclude the patient's ability to tolerate
             protocol therapy.

          6. Predicted survival less than 3 months.

          7. Previous allergic reaction to Montanide Adjuvant.

          8. Pregnant or breast feeding (Pregnant and breast-feeding women are excluded from study
             because the effects of vaccination are not known and may pose a risk to the developing
             fetus. All female patients will have a urine pregnancy test, and only those that test
             negative will be allowed on study).

          9. Enrolled in another vaccine clinical trial during the study period.

         10. Inability to comprehend the investigational nature of the study and provide informed
             consent.

        Exclusion Criteria-Donor (any of the following):

          1. Pregnant or lactating.

          2. Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts,
             history of stroke, uncontrolled hypertension).

          3. HIV positive.

          4. Severe psychiatric illness. Mental deficiency sufficiently severe as to make
             compliance with the bone marrow transplant (BMT) treatment unlikely and making
             informed consent impossible.