Myelodysplastic Syndromes
Conditions
Keywords
refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, refractory cytopenia with multilineage dysplasia, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes
Brief summary
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with GM-CSF works in treating patients with low-risk or intermediate-risk myelodysplastic syndrome.
Detailed description
OBJECTIVES: Primary * To determine the immunologic response, using a PR1-HLA-A2 tetramer assay, to 4 subcutaneous injections of PR1 leukemia peptide vaccine formulated in incomplete Freund's adjuvant (IFA) followed by sargramostim (GM-CSF) in patients with low- and intermediate-1-risk myelodysplastic syndromes. Secondary * To determine if non-immunologic responders to 4 subcutaneous injections of PR1 leukemia peptide vaccine formulated in IFA followed by GM-CSF can be converted to immunologic responders by administering 4 additional doses of this treatment. * To determine the clinical response to 4 or 8 subcutaneous injections of this vaccine. OUTLINE: This is a multicenter study. Patients will receive proteinase PR1 leukemia peptide vaccine (TVC-PR1) conjugated with incomplete Freund's adjuvant administered subcutaneously with sargramostim (GM-CSF). Patients will receive a series of four vaccinations at 3-week intervals. Non-immunologic responders after 4 doses of vaccine are eligible to receive 4 additional doses of TVC-PR1 vaccine with the same dose and same dosing intervals. Patients who mount an immunologic response after 4 doses will not receive additional doses of TVC-PR1 vaccine. After completion of study therapy, patients are followed monthly for up to 6 months.
Interventions
Sponsors
The Vaccine Company
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Diagnosis of myelodysplastic syndromes (MDS) and must meet all of the following criteria: * FAB class refractory anemia (RA), RA with excess blasts (RAEB), or RA with ringed sideroblasts (RARS) * WHO Classification RA, RARS, refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts, or RAEB-1 * Less than 20% blasts on marrow aspirate * IPSS risks groups intermediate-1- OR transfusion dependent low-risk * Patients with de novo or therapy-related MDS eligible * HLA-A2 positive at one allele
Exclusion criteria
* RAEB in transformation or RAEB-2 * Chloroma * Marrow blasts on aspirate ≥ 20% * Blood blasts \> 1% * Inaspirable bone marrow * History or current myelosclerosis occupying \> 30% of marrow space * History of acute myeloid leukemia * Other causes of cytopenia not related to MDS (i.e., gastrointestinal blood loss) PATIENT CHARACTERISTICS: Inclusion criteria: * ECOG performance status 0 or 1 * Women of childbearing potential must have a negative serum pregnancy test within 30 days of starting study drug * Male or female of child-bearing potential must agree to use adequate contraceptive methods * Serum bilirubin \< 2 mg/mL * Creatinine ≤ 1.5 mg/mL * ALT \< 2 times upper normal limit * Antineutrophil cytoplasmic antibody (cANCA) negative
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunologic response after four injections of vaccine formulation as determined by an increase in the absolute PR1-HLA-A2 tetramer count by at least 0.5/μl | — |
Secondary
| Measure | Time frame |
|---|---|
| Conversion of non-immunologic responders to immunologic responders by administering 4 additional doses of vaccine | — |
| Clinical response as determined by modified IWG criteria | — |
Countries
United States
Outcome results
None listed