Safety Assessment of a Multipeptide-gene Vaccine in CML - Full Text View

Sponsor:	Tehran University of Medical Sciences
Information provided by:	Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT00455221

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 I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
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:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Imatinib

U.S. FDA Resources

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 ]

Estimated Enrollment:	12
Study Start Date:	February 2008
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Peptide Vaccine: Experimental	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

Arms

Assigned Interventions

Peptide Vaccine: Experimental

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

Contacts

Contact: Seyed Hamidollah Ghaffari, PhD	+98-21-8490 2626	horcbmt@sina.tums.ac.ir
Contact: Monireh Asadi, B.Sc	+98-21-8490 2628	horcbmt@sina.tums.ac.ir

Locations

Iran, Islamic Republic of
Hematology-Oncology & SCT Research Center	Recruiting
Tehran, Iran, Islamic Republic of, 14114
Contact: Seyed Hamidollah Ghaffari, PhD +98-21-84902635
Principal Investigator: Seyed Hamidollah Ghaffari, PhD

Sponsors and Collaborators

Tehran University of Medical Sciences

Investigators

Principal Investigator:

Seyed Hamidollah Ghaffari, PhD

Tehran University of Medical Sciences

More Information

Additional Information:

Hematology-Oncology & SCT Research Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Deputy of Research in Tehran University of Medical Sciences ( Deputy of Research )
Study ID Numbers:	418-A-2209
Study First Received:	March 31, 2007
Last Updated:	November 17, 2009
ClinicalTrials.gov Identifier:	NCT00455221 History of Changes
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
Neoplasms
Neoplasms by Histologic Type
Hematologic Diseases

Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases

ClinicalTrials.gov processed this record on February 08, 2010