Safety Assessment of a Multipeptide-gene Vaccine in CML
Condition: Leukemia, Myeloid, Chronic
MeSH terms: Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      -  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.
    

Intervention name(s): Bcr-abl multipeptide vaccine; Cytokine gene adjuvant
Intervention type(s): Biological; Genetic
Intervention description(s): 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; Cytokine gene adjuvant
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CML; Imatinib; vaccine; peptide; gene; MRD; DNA