Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors
Condition: Cytomegalovirus Infections
MeSH terms: Cytomegalovirus Infections
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Cytomegalovirus (CMV) infection is a major complication following allogeneic stem cell
      transplantation (SCT). The risk of CMV infection after SCT is inversely related to the number
      of CMV-specific cytotoxic T-lymphocytes (CTLs) present in the allograft. CMV-specific
      lymphocytes can be readily detected and quantified in the blood by sensitive in vitro
      techniques that measure T cell cytokine secretion following antigen stimulation. A previous
      phase I clinical trial has demonstrated that CMV-specific T cells can be safely generated in
      normal CMV-seronegative (naive) subjects after immunization with the CMV vaccine, ALVAC-pp65
      (vCP260), an attenuated canary pox-based vaccine Sanofi Pasteur (formerly known as Aventis
      Pasteur, Lyon, France).

      We propose a clinical trial to evaluate an accelerated immunization schedule with the same
      vaccine. Study participants will be 1) SCT donors and their matched recipients participating
      in intramural NIH allogeneic SCT protocols and 2) CMV sero-negative normal volunteers. Donors
      will receive two or three immunizations prior to allograft collection, and followed for 45
      days for the development of CMV immunity. Normal volunteers will receive two or three
      immunizations and followed similarly to the donors. CMV sero-positive subjects will receive
      two immunizations; CMV sero-negative subjects will receive three. Transplant (SCT) recipients
      will be evaluated for incidence of CMV infection and disease.

      The study is designed as a two-stage phase II trial with stopping rules at each stage. The
      primary outcome measures are the effectiveness of the vaccine in (a) generating cellular
      immunity in CMV-seronegative (naive) donors or CMV sero-negative normal volunteers and (b)
      boosting the cellular immune response in CMV-seropositive (sensitized) donors and healthy
      volunteers. Secondary outcomes include the clinical safety profile of the vaccine in vaccine
      recipients and the incidence of CMV infection/disease in transplant recipients. Since the
      cellular immune response to CMV is a standard model for immune reconstitution post
      transplant, our study may also provide important information on the feasibility of immunizing
      stem cell transplant donors with other microbial and tumor vaccines.
    

Intervention name(s): ALVAC-CMV (vCP260)
Intervention type(s): Biological
Intervention description(s): 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.)
Other intervention name(s): Canary Pox CMV vaccine
Intervention MeSH terms: Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Cytomegalovirus; Vaccine; CMV; Immunization; Peripheral Blood Stem Cell Transplantation; Stem Cell Allotransplant