Cytomegalovirus InfectionsPhase 2NCT00353977
Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors
A Phase 2 study testing ALVAC-CMV (vCP260) in people with Cytomegalovirus Infections, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- ALVAC-CMV (vCP260)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Mar 2008
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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)
- STEM CELL TRANSPLANT RECIPIENT
- There are no exclusion criteria for stem cell transplant recipients
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Trial of an Accelerated Immunization Schedule With ALVAC-pp65 (vCP260) for Inducing CMV-Specific Immunity in Stem Cell Allotransplant Donors and Healthy Volunteers
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.
Read more
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.
Read the 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.
- Conditions
- Cytomegalovirus Infections
- Being tested
- ALVAC-CMV (vCP260)
- Keywords
- Cytomegalovirus, Vaccine, CMV, Immunization, Peripheral Blood Stem Cell Transplantation, Stem Cell Allotransplant
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALVAC-CMV (vCP260)Biological
Also called Canary Pox CMV vaccine
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.)
| Study group | Role | What they receive |
|---|---|---|
| ALVAC-CMV (vCP260) Vaccinated group | Experimental | Patients who were vaccinated with ALVAC-CMV (vCP260) Receives: Biological: ALVAC-CMV (vCP260) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular Immune Response in Vaccine Recipients
Evaluate the efficacy of an accelerated ALVAC-pp65 immunization schedule in generating cytomegalovirus (CMV)-specific immunity in seronegative transplant donors and healthy volunteers (HV) and augmenting CMV-specific immunity in seropositive transplant donors.
Measured: Day 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2006 (estimated)
- Study startMay 2004
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Minoo Battiwalla, M.D., National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Minocher Battiwalla, MD, Principal investigator, National Institutes of Health- NHLBI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00353977
- Sponsor's protocol ID
- 040198
- Other IDs
- 04-H-0198
- Status last verified
- Jun 2014
- First submitted
- 18 Jul 2006
- Last updated
- 8 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gerberding JL. Incidence and prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and cytomegalovirus among health care personnel at risk for blood exposure: final report from a longitudinal study. J Infect Dis. 1994 Dec;170(6):1410-7. doi: 10.1093/infdis/170.6.1410.
PubMed 7995979Bevan IS, Daw RA, Day PJ, Ala FA, Walker MR. Polymerase chain reaction for detection of human cytomegalovirus infection in a blood donor population. Br J Haematol. 1991 May;78(1):94-9. doi: 10.1111/j.1365-2141.1991.tb04388.x.
PubMed 1645986Bolovan-Fritts CA, Mocarski ES, Wiedeman JA. Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood. 1999 Jan 1;93(1):394-8.
PubMed 9864186