Safety Assessment of a Multipeptide-gene Vaccine in CML
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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Patients will continue to take their current dose of Imatinib.
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Patients will undergo HLA-typing to define the HLA A, B, and DR.
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One constant dose of ten bcr-abl peptides (100μg each) will be administered subcutaneously in all patients triweekly for 8 doses.
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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.
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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.
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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.
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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.
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Patients will also undergo DTH skin tests before and after vaccination to see if an immune reaction is occurring at the injection site.
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Patients' lymphocytes will be tested before and after vaccination regarding IFN-γ and IL-4 production to assess immune system activation.
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During the course of treatment we will measure the effect the vaccine is having on the patients CML every three months by:
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doing a bone marrow biopsy and aspirate analysis, and
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measuring the amount of BCR-ABL that is detectable by RT-PCR in the patients' peripheral blood and bone marrow aspirate.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Peptide Vaccine
|
Biological: Bcr-abl multipeptide vaccine
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
Genetic: Cytokine gene adjuvant
Cytokine gene adjuvant
|
Outcome Measures
Primary Outcome Measures
- To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients [At enroll in study and 3 months after intervention]
Secondary Outcome Measures
- To measure the development of a molecular response to vaccination as measured by 1 log decrease in qRT-PCR BCR-ABL levels for at least 3 months; To measure the development of immune response following vaccination [At enroll in study and 3 months after intervention]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients with Philadelphia chromosome positive CML who are:
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of subtype b3a2
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In first complete hematologic response;
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have received imatinib for > 12 months of which the last 3 months were at a stable dose of at least 400 mg/day;
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have PCR detectable BCR-ABL transcript by qRT-PCR, and
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with persistent disease, as defined by <1 log reduction in peripheral blood or bone marrow BCR-ABL transcripts levels compared with a standardized baseline.
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Greater than or equal to 18 years in age
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No known infection with human immunodeficiency virus
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Physician and patient willingness to maintain the baseline dose of imatinib throughout the study period
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Written informed consent obtained from the patient
Exclusion Criteria:
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Female patients who are pregnant or breast feeding or adults of childbearing age who are not using adequate birth control.
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Current use of systemic immunosuppressive medications
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ALT or AST >3X Upper limit Normal
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Prior allogeneic stem cell transplantation
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Other experimental therapy within the past two months
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Prior participation in vaccine studies within the past six months
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Oxygen saturation of less than 95% at room air
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History of recent acute myocardial infarction, unstable angina, or pulmonary decompensation requiring hospitalization within the past 3 months.
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Concurrent and or uncontrolled psychiatric or medical condition which may interfere with the study completion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hematology-Oncology & SCT Research Center | Tehran | Iran, Islamic Republic of | 14114 |
Sponsors and Collaborators
- Tehran University of Medical Sciences
Investigators
- Principal Investigator: Seyed Hamidollah Ghaffari, PhD, Tehran University of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 418-A-2209