Safety Assessment of a Multipeptide-gene Vaccine in CML

NCT ID: NCT00455221

Last Updated: 2012-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2011-11-30

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.

Conditions

Leukemia, Myeloid, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Peptide Vaccine

Group Type: EXPERIMENTAL

Bcr-abl multipeptide vaccine

Intervention Type: BIOLOGICAL

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

Cytokine gene adjuvant

Intervention Type: GENETIC

Cytokine gene adjuvant

Interventions

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

Intervention Type: BIOLOGICAL

Cytokine gene adjuvant

Cytokine gene adjuvant

Intervention Type: GENETIC

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tehran University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seyed Hamidollah Ghaffari, PhD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Locations

Hematology-Oncology & SCT Research Center

Tehran, Tehran Province, Iran

Countries

Iran

Other Identifiers

418-A-2209

Identifier Type: -

Identifier Source: org_study_id