Safety Assessment of a Multipeptide-gene Vaccine in CML

Leukemia, Myeloid, Chronic Clinical Trial

Official title:

Safety Assessment of a Peptide Vaccine Derived From Bcr-abl Along With Cytokine Genes in CML Patients Undergoing Imatinib Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00455221
• Other study ID #: 418-A-2209
• Status: Completed
• Phase: Phase 1
• First received: March 31, 2007
• Last updated: May 31, 2012
• Start date: February 2008
• Est. completion date: November 2011

Study information

• Verified date: May 2012
• Source: Tehran University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic

Intervention

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

Locations

Country	Name	City	State
Iran, Islamic Republic of	Hematology-Oncology & SCT Research Center	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients		At enroll in study and 3 months after intervention	Yes
Secondary	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		At enroll in study and 3 months after intervention	No

External Links

•   Hematology-Oncology & SCT Research Center