Safety Assessment of a Multipeptide-gene Vaccine in CML

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Chronic
• Intervention / Treatment: Biological: Bcr-abl multipeptide vaccine; Genetic: 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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 14114
    • Hematology-Oncology & SCT Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Peptide Vaccine

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Seyed Hamidollah Ghaffari, PhD, Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 31, 2007
• First Submitted That Met QC Criteria: March 31, 2007
• First Posted (Estimate): April 3, 2007

Study Record Updates

• Last Update Posted (Estimate): June 4, 2012
• Last Update Submitted That Met QC Criteria: May 31, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: DNA; vaccine; CML; Imatinib; MRD; peptide; gene
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: 418-A-2209