Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors

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.

• 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