Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
Condition: Myelodysplastic Syndrome (MDS); Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Syndrome
Intervention: WT1:126-134; PR1:169-177 Peptide; GM-CSF (Sargramostim); Montanide adjuvant
Intervention description: Subjects were given 6 doses of PR1:169-177 in "Montanide" adjuvant and 6 doses of WT1:126-134 in "Montanide" adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.; Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.; Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.; Subjects were given 6 doses of PR1:169-177 in montanide adjuvant and 6 doses of WT-1:126-134 in Montanide adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
Intervention MeSH terms: Molgramostim; Sargramostim; Monatide (IMS 3015)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Myelodysplastic 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

Summary:

      This study will test the safety and effectiveness of two vaccines on slowing disease
      progression, improving blood counts, reducing the need for transfusions of blood and
      platelets, or achieving remission in patients with myelodysplastic syndrome (MDS, also known
      as myelodysplasia), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML). The
      vaccines consist of peptides (parts of proteins) found in MDS, AML and CML stem cells,
      combined with a substance called "MontanideTM". They are administered with granulocyte-
      macrophage colony- stimulating factor (GM-CSF). The Montanide and the GM-CSF help the immune
      system respond to the vaccines.

      People 18 years of age or older with MDS, AML or CML may be eligible for this study.

      Participants receive six injections of the vaccines, one dose every other week for a total of
      10 weeks. The injections are given in the upper arm, upper leg, or abdomen. A separate
      injection of GM-CSF is given in the same area as the vaccine injections. Subjects are
      observed for 2 hours after the first vaccination and at least 30 minutes after each
      subsequent vaccination for allergic reactions. In addition to the vaccination, subjects
      undergo the following:

        -  History and physical exam, chest x-ray, blood tests and bone marrow aspirate and biopsy
           before starting the vaccinations.

        -  Safety monitoring during vaccine administration (every other week for 10 weeks) with
           blood tests and check of vital signs.

        -  Follow-up safety monitoring (weeks 12 and 16) with blood tests every visit, chest x-ray
           at week 12 and bone marrow biopsy visit 16.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Diagnosed with MDS (B subtypes Refractory anemia (RA), Refractory anemia with ring
        sideroblasts (RARS) -Low Risk) (MDS with 5q- must have failed lenalidomide or been
        ineligible to receive it)

        OR

        Diagnosed with AML and in complete remission within 5 years of treatment with less than 5%
        marrow blasts

        OR

        Diagnosed with CML in chronic phase

        Unsuitable for stem cell transplantation (SCT) (age over sixty or unavailability of a
        fully-matched donor)

        or

        made an informed decision not to undergo the transplant procedure

        or

        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

        Human leukocyte antigen (HLA-A020 1) positive at one allele

        Ages 18-85 years old

        Off all lympho-ablative chemotherapeutic agents

        EXCLUSION CRITERIA:

          -  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 immunosuppressants within 14 days prior to
             study entry

          -  Co-morbidity 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
             consent