Safety Assessment of a Peptide Vaccine Derived From Bcr-abl Along With Cytokine Genes in CML Patients Undergoing Imatinib Treatment
18 Years
65 Years
Both
Leukemia, Myeloid, Chronic
Trial Information
Safety Assessment of a Peptide Vaccine Derived From Bcr-abl Along With Cytokine Genes in CML Patients Undergoing Imatinib Treatment
- 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.
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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients
Outcome Time Frame:
At enroll in study and 3 months after intervention
Safety Issue:
Yes
Principal Investigator
Seyed Hamidollah Ghaffari, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Tehran University of Medical Sciences
Authority:
Iran: Ministry of Health
Study ID:
418-A-2209
NCT ID:
NCT00455221
Start Date:
February 2008
Completion Date:
November 2011
Related Keywords:
- Leukemia, Myeloid, Chronic
- CML
- Imatinib
- vaccine
- peptide
- gene
- MRD
- DNA
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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