safety assessment of a multipeptide-gene vaccine in cml

Conditions: Leukemia, Myeloid, Chronic

Summary: the primary purpose of this study is to evaluate the safety of a peptide-gene vaccine against cml in patients under imatinib treatment. we will also perform some laboratory tests suggesting biological response.

* patients will continue to take their current dose of imatinib. * patients will undergo hla-typing to define the hla a, b, and dr. * one constant dose of ten bcr-abl peptides (100μg each) will be administered subcutaneously in all patients triweekly for 8 doses. * four different doses of il-12 and gm-csf plasmids will be tested in this trial. the plasmids will be administered subcutaneously near the vaccination site 24 hours before vaccination. * the first three patients will receive the lower dose of both il-12 and gm-csf plasmids. if this is well tolerated, then the next three patients will receive the lower dose of il-12 plasmid and higher dose of gm-csf plasmid. if this is well tolerated, then the next three patients will receive the higher dose of il-12 and lower dose of gm-csf plasmids. if this is well tolerated, then the next three patients will receive the higher dose of both il-12 and gm-csf plasmids. once assigned to a dose, the patient will receive the same dose throughout their participation in this trial. * each vaccination may consist of one to several shots placed under the skin on the forearm, thigh or trunk area, and the sites will rotate per vaccination. * during the clinic visit for vaccinations, blood tests will be drawn. if, during the course of therapy, side effects develop that the doctor feels pose a threat to the patient, treatment will be stopped. * patients will also undergo dth skin tests before and after vaccination to see if an immune reaction is occurring at the injection site. * patients' lymphocytes will be tested before and after vaccination regarding ifn-γ and il-4 production to assess immune system activation. * during the course of treatment we will measure the effect the vaccine is having on the patients cml every three months by: 1. doing a bone marrow biopsy and aspirate analysis, and 2. measuring the amount of bcr-abl that is detectable by rt-pcr in the patients' peripheral blood and bone marrow aspirate.

Eligibility criteria:
inclusion criteria: * patients with philadelphia chromosome positive cml who are: 1. of subtype b3a2 2. in first complete hematologic response; 3. have received imatinib for \> 12 months of which the last 3 months were at a stable dose of at least 400 mg/day; 4. have pcr detectable bcr-abl transcript by qrt-pcr, and 5. with persistent disease, as defined by \<1 log reduction in peripheral blood or bone marrow bcr-abl transcripts levels compared with a standardized baseline. * greater than or equal to 18 years in age * no known infection with human immunodeficiency virus * physician and patient willingness to maintain the baseline dose of imatinib throughout the study period * written informed consent obtained from the patient exclusion criteria: * female patients who are pregnant or breast feeding or adults of childbearing age who are not using adequate birth control. * current use of systemic immunosuppressive medications * alt or ast \>3x upper limit normal * prior allogeneic stem cell transplantation * other experimental therapy within the past two months * prior participation in vaccine studies within the past six months * oxygen saturation of less than 95% at room air * history of recent acute myocardial infarction, unstable angina, or pulmonary decompensation requiring hospitalization within the past 3 months. * concurrent and or uncontrolled psychiatric or medical condition which may interfere with the study completion.

Keywords: cml imatinib vaccine peptide gene mrd dna