Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors
Condition: Cytomegalovirus Infections
MeSH terms: Cytomegalovirus Infections
Intervention: ALVAC-CMV (vCP260)
Intervention description: ALVAC-pp65 (vCP260), an attenuated canary pox-based vaccine (Aventis Sanofi Pasteur, Lyon, France), 3 doses (1.0 ml each) delivered intramuscularly in the deltoid muscle.
Sero-negative subjects will receive a total of 3 immunizations to be given day 0, 5 and 10.
Sero-positive subjects will receive a total of 2 immunizations to be given day 0 and 5. (Protocol amendment after findings from the 9/6/2006 interim analysis demonstrated that in the sero-positive group, only 2 vaccinations were required to generate maximum immune response.)
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Cytomegalovirus; Vaccine; CMV; Immunization; Peripheral Blood Stem Cell Transplantation; Stem Cell Allotransplant

Summary:

      This study will evaluate the safety and effectiveness of a new vaccine, ALVAC-pp65, in
      boosting immunity to cytomegalovirus (CMV) infection in stem cell transplant donors. CMV is a
      member of the herpesvirus group, which includes herpes simplex virus types 1 and 2,
      varicella-zoster virus (which causes chickenpox), and Epstein-Barr virus (which causes
      infectious mononucleosis). Most adults are infected with CMV, but a healthy immune system
      keeps the virus in check, so that it does not cause harm. In people with a weakened immune
      system, such as transplant recipients, the virus can become reactivated. Medications for
      treating the infection may cause low blood counts and kidney damage, and, in some cases, the
      virus may cause death. The ALVAC-pp65 vaccine is intended to improve immunity against CMV in
      stem cell donors and thereby prevent its reactivation in recipients. It is made from a virus
      that ordinarily infects canaries. The virus is weakened so that it cannot infect the person
      who receives it, and it is modified to carry a copy of a CMV gene called pp65. This gene
      instructs cells to make CMV proteins that the vaccine recipient's immune system can produce
      antibodies to, thus conferring immunity to the disease.

      Persons 18 years of age or older who are scheduled to donate stem cells for a patient in an
      NIH protocol and who are not allergic to eggs, egg products, or other vaccines, may be
      eligible for this study. Candidates are screened with a medical history, physical
      examination, and blood tests.

      Participants receive three vaccinations one week apart beginning at least 3 weeks before the
      scheduled stem cell donation. They are observed for 30 minutes after each vaccination to look
      for any immediate side effects of the vaccine. Approximately 3 tablespoons of blood are drawn
      before each vaccination and 1 week after the last vaccination to evaluate vaccine safety.
      Blood samples are also collected at the screening evaluation, 3 weeks after the start of
      vaccination, and 3 months after the last vaccination to check for CMV immunity.

      Participants keep a diary, recording any reactions to the vaccine and any change in
      medications. They are contacted by telephone for follow-up 3 months after the last
      vaccination to report any additional symptoms.
    

Eligibility criteria:

        - INCLUSION CRITERIA: VACCINE RECIPIENT

          -  Under evaluation for enrollment as a donor on a stem cell transplant protocol at the
             NIH Clinical Center, Or

          -  CMV sero-negative or sero-positive healthy volunteer

          -  Age greater than or equal to 18 years, but less than or equal to 80 years

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent

          -  All subjects (men and women) must agree to practice abstinence or effective
             contraception during the study period

          -  Baseline laboratory evaluations are within normal limits

          -  For woman, negative urinary pregnancy test

          -  Informed consent from transplant recipients obtained

          -  INCLUSION CRITERIA:

        STEM CELL TRANSPLANT RECIPIENT

          -  Under evaluation for enrollment as a recipient on a stem cell transplant protocol at
             the NIH

          -  Age greater than or equal to 18 years, and less than or equal to 75 years

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent

          -  EXCLUSION CRITERIA:

        VACCINE RECIPIENT

          -  History of severe adverse reaction or allergy to any vaccine

          -  Known or suspected allergies to vaccine constituents - eggs, mono-sodium glutamate or
             neomycin

          -  Acute febrile illness within the 72 hours preceding the vaccination

          -  History of any immunosuppressive disease or major chronic disorder

          -  History of treatment with immunosuppressive medications in the past 6 months

          -  Pregnant or breast feeding

          -  Enrolled or planning to enroll in another drug or vaccine clinical trial during the
             study period (other than the stem cell transplant when applicable)

          -  EXCLUSION CRITERIA:

        STEM CELL TRANSPLANT RECIPIENT

        - There are no exclusion criteria for stem cell transplant recipients