Safety Assessment of a Multipeptide-gene Vaccine in CML

Tehran University of Medical Sciences

Status and phase

Completed

Phase 1

Conditions

Leukemia, Myeloid, Chronic

Treatments

Genetic: Cytokine gene adjuvant

Biological: Bcr-abl multipeptide vaccine

Study type

Interventional

Funder types

Other

Identifiers

NCT00455221

418-A-2209

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.