Safety Assessment of a Multipeptide-gene Vaccine in CML

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT00455221
First received: March 31, 2007
Last updated: May 31, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Leukemia, Myeloid, Chronic
Biological: Bcr-abl multipeptide vaccine
Genetic: Cytokine gene adjuvant
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety Assessment of a Peptide Vaccine Derived From Bcr-abl Along With Cytokine Genes in CML Patients Undergoing Imatinib Treatment

Resource links provided by NLM:


Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:
  • To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients [ Time Frame: At enroll in study and 3 months after intervention ] [ Designated as safety issue: Yes ]

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 [ Time Frame: At enroll in study and 3 months after intervention ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: February 2008
Study Completion Date: November 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455221

Locations
Iran, Islamic Republic of
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
  More Information

Additional Information:
No publications provided

Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT00455221     History of Changes
Other Study ID Numbers: 418-A-2209
Study First Received: March 31, 2007
Last Updated: May 31, 2012
Health Authority: Iran: Ministry of Health

Keywords provided by Tehran University of Medical Sciences:
CML
Imatinib
vaccine
peptide
gene
MRD
DNA

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on April 15, 2014