Safety Assessment of a Multipeptide-gene Vaccine in CML

Phase 1

Completed

• Conditions: Leukemia, Myeloid, Chronic
• Interventions: Biological: Bcr-abl multipeptide vaccine; Genetic: Cytokine gene adjuvant

• Registration Number: NCT00455221
• Lead Sponsor: Tehran University of Medical Sciences

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.

Study Timeline

• Study First Submitted: 2007-03-31
• Study First Submitted QC: 2007-03-31
• Study First Posted: 2007-04-03
• Study Start: 2008-02
• Primary Completion: 2010-12
• Study Completion: 2011-11
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-31
• Last Update Posted: 2012-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Peptide Vaccine	Bcr-abl multipeptide vaccine	-
Peptide Vaccine	Cytokine gene adjuvant	-

Primary Outcome Measures

Name	Time	Method
To assess safety of bcr-abl peptide vaccination in Ph+ or MRD CML patients	At enroll in study and 3 months after intervention

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hematology-Oncology & SCT Research Center; 🇮🇷 Tehran, Iran, Islamic Republic of