PR1 Vaccination in Myelodysplastic Syndrome (MDS)
Condition: Leukemia; Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: PR-1 vaccine
Intervention description: 0.5 mg injections under the skin once every 3 weeks for a total of 4 vaccinations.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myelodysplastic syndrome; MDS; PR1 Peptide Vaccine

Summary:

      Primary aim:

        1. To determine the immunologic response, using a PR1-HLA-A2 tetramer assay, to 4
           subcutaneous (SQ) injections of TVC-PR1 vaccine formulated in Montanide ISA 51 VG
           followed by granulocyte macrophage colony-stimulating factor (GM-CSF) in low risk and
           intermediate-1 myelodysplastic syndrome (MDS) patients.

      Secondary aims:

        1. To determine if non-immunologic responders to 4 subcutaneous (SQ) injections of TVCPR1
           vaccine formulated in Montanide ISA 51 VG followed by GM-CSF can be converted to
           immunologic responders by administering 4 additional doses of TVC-PR1 vaccine formulated
           in Montanide ISA 51 VG followed by GM-CSF.

        2. To determine the clinical response to 4 or 8 subcutaneous (SQ) injections of TVC-PR1
           vaccine formulated in Montanide ISA 51 VG followed by GM-CSF in patients low risk and
           intermediate-1 MDS.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must understand and voluntarily sign an informed consent form

          2. Age >/= 18 years at the time of signing the informed consent form

          3. Must be able to adhere to the study visit schedule and other protocol requirements

          4. HLA-A2 positive at one allele

          5. Diagnosis of myelodysplastic syndrome (MDS) and must meet all the following criteria

          6. French-American-British (FAB) Class Refractory anemia (RA), Refractory Anemia with
             Excess Blasts (RAEB), refractory anemia with ringed sideroblasts (RARS)

          7. World Health Organization(WHO) Classification refractory anemia (RA), refractory
             anemia with ringed sideroblasts(RARS), refractory cytopenia with multilineage
             dysplasia (RCMD), refractory cytopenia with ringed sideroblasts (RCMD-RS) , refractory
             anemia with excess blasts type 1 (RAEB-1)

          8. Less than 20% blasts on marrow aspirate

          9. International Prognostic Scoring System (IPSS) risk groups Intermediate 1 or
             transfusion dependent low risk.

         10. Both de novo and therapy related MDS are eligible

         11. Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1

         12. Women of childbearing potential must have a negative serum pregnancy test within 30
             days of starting study drug. A woman of child-bearing potential is a sexually mature
             woman who has not undergone a hysterectomy or who has not been naturally
             postmenopausal for at least 24 consecutive months (i.e., who has had menses at any
             time in the preceding 24 consecutive months)

         13. Male or female of child-bearing potential must agree to use adequate contraceptive
             methods

         14. Serum bilirubin < 2 mg/ml

         15. Serum creatinine </= 1.5 mg/ml

         16. Serum ALT < 2 x upper normal limit

         17. anti-neutrophil cytoplasmic antibody (cANCA) negative

         18. Not received specific therapy for MDS for 4 weeks. However, supportive therapy is
             permitted.

        Exclusion Criteria:

          1. Marrow blasts on aspirate >/= 20%

          2. Blood blasts > 1%

          3. Inaspirable bone marrow

          4. Myelosclerosis occupying >30% of marrow space

          5. Iron absence on marrow examination or transferrin saturation <20% and serum ferritin
             <50ng/ml

          6. B-12 deficiency

          7. Folate deficiency

          8. History of immune related hematological disorder [i.e.,immune thrombopenia
             purpura(ITP),autoimmune hemolytic anemia ( AIHA)]

          9. Other causes of cytopenia not related to MDS (i.e., GI blood loss)

         10. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form or that will place
             the subject at unacceptable risk if he/she were to participate in the study or
             confounds the ability to interpret the data

         11. Prior allogeneic or syngeneic transplant

         12. Prior solid organ transplant

         13. Life expectancy severely limited by diseases other than MDS

         14. Pregnant or lactating females

         15. Prior vaccine therapy for MDS

         16. Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent
             (dose equivalent to >10 mg/day of prednisone) within 30 days of the first day of study
             drug treatment. (Topical and inhaled corticosteroids are permitted)

         17. Prior history of malignancy other than MDS (except basal cell or squamous cell
             carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been
             free of disease for >/= 5 years

         18. Known allergy to incomplete Freund's adjuvant

         19. Experimental therapy, cyclosporine, antithymocyte globulin, or FK506 within 3 months
             of study entry

         20. Treatment with androgenic hormones, danazol, colony stimulating factors,
             erythropoietin, thalidomide, arsenic trioxide or other agents used to treat MDS within
             four weeks of the first day of study treatment

         21. refractory anemia with excess blasts in transformation (RAEB-t) (French-American
             British (FAB) criteria ) or refractory anemia with excess blasts type2 (RAEB-2) (World
             Health Organization (WHO) criteria)

         22. Chloroma

         23. Hypercalcemia

         24. Progressive viral or bacterial infection. Patients are not eligible unless all
             infections are resolved and the patient has remained afebrile for seven days without
             antibiotics

         25. Cardiac disease of symptomatic nature or cardiac ejection fraction < 40%

         26. Symptomatic pulmonary disease or FEV1, FVC and Carbon Monoxide Diffusing Capacity
             (DLCO) </= 50% predicted

         27. History of Wegener's Granulomatosis or vasculitis

         28. History of HIV positivity or AIDS

         29. Prior history of AML