Safety Assessment of a Multipeptide-gene Vaccine in CML

Tehran University of Medical Sciences12 enrolled

Overview

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.

* 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Myeloid, Chronic

Interventions

Bcr-abl multipeptide vaccineBIOLOGICAL

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 adjuvantGENETIC

Cytokine gene adjuvant

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (1)

Hematology-Oncology & SCT Research Center

Tehran, Tehran Province, Iran

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

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