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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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Leukemia
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 27, 2014