Clinical trial NCT00455221: Safety Assessment of a Multipeptide-gene Vaccine in CML
Official title: Safety Assessment of a Peptide Vaccine Derived From Bcr-abl Along With Cytokine Genes in CML Patients Undergoing Imatinib Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Chronic
Keywords: CML
Imatinib
vaccine
peptide
gene
MRD
DNA
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2007-04-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients
timeFrame: At enroll in study and 3 months after intervention
Secondary outcomes:
measure: 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
timeFrame: At enroll in study and 3 months after intervention
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Hematology-Oncology & SCT Research Center
Study officials:
affiliation: Tehran University of Medical Sciences
name: Seyed Hamidollah Ghaffari, PhD
role: PRINCIPAL_INVESTIGATOR
References: