Cytomegalovirus Vaccine in Healthy Participants

A Phase I Dose Escalation Study of Lipopeptide Vaccines With Activity Against Human Cytomegalovirus

RATIONALE: Vaccines may help the body build an effective immune response against cytomegalovirus.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of cytomegalovirus vaccine in healthy participants.

Study Overview

• Status: Completed
• Conditions: Precancerous/Nonmalignant Condition
• Intervention / Treatment: Biological: CMVpp65-A*0201 peptide vaccine

Detailed Description

OBJECTIVES:

• To establish whether 4 dose levels of the CMVpp65-A*0201 peptide vaccine are safe and well tolerated in cytomegalovirus (CMV)-seropositive participants.
• To determine whether the CMVpp65-A*0201 peptide vaccine, when given as a single injection followed by one booster injection at a safe and well-tolerated dose, is capable of stimulating a memory response in CMV-seropositive participants.
• To evaluate whether CMV-seronegative participants generate a de novo immune response against CMV after immunization with CMVpp65-A*0201 peptide vaccine given as a single injection followed by three booster injections.
• To determine the duration of immune enhancement of CMV-specific cytotoxic T-lymphocyte function as assessed for up to 12 months after primary or secondary immunization with the CMVpp65-A*0201 peptide vaccine.

OUTLINE: This is a dose-escalation study of CMVpp65-A*0201 peptide vaccine in cytomegalovirus (CMV)-seropositive participants. Once a safe dose is established, CMV-seronegative participants are accrued and immunized at that dose. Participants are stratified according to gender.

• CMV-seropositive participants: Participants are randomized to receive 1 of 4 escalating doses of CMVpp65-A*0201 peptide vaccine containing either helper T-lymphocyte (HTL) PADRE peptide or HTL tetanus toxoid peptide. Within each vaccine dose group, two participants are randomized to receive a placebo. Participants receive the vaccine or a placebo subcutaneously (SC) on days 0 and 28 in the absence of unacceptable toxicity.
• CMV-seronegative participants: Participants are randomized to receive 1 of 4 established doses (established in CMV-seropositive participants) of CMVpp65-A*0201 peptide vaccine containing either HTL PADRE peptide or HTL tetanus toxoid peptide. Participants receive the vaccine on days 0, 28, and 56 in the absence of unacceptable toxicity. Participants with a partial or low-level immune response receive one additional booster vaccine on day 90.

Participants undergo blood sample collection at baseline and periodically during study for immunologic laboratory studies. Participants also undergo skin biopsy at baseline. Laboratory studies include assessment of human cytotoxic T-lymphocyte activity and response by ^51chromium-release assay, limiting-dilution analysis, and T-cell proliferation assay; and CD4/CD8 phenotyping by FACScan® flow cytometry.

After completion of study therapy, participants are followed for 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Healthy participant
• Cytomegalovirus seropositive or seronegative
• HLA-A*0201-positive

PATIENT CHARACTERISTICS:

• CBC within 1.5 times normal
• SMA-18 within 1.5 times normal
• Hepatitis B virus antigen seronegative
• Hepatitis C virus seronegative
• No diagnosis that is associated with immunodeficiency, including HIV infection
• No serious abnormalities by EKG (in participants ≥ 50 years of age)
• Not pregnant

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior surgery

• No concurrent daily medications for chronic or current illness, except for the following:

  • Thyroid replacement therapy
  • Estrogen replacement therapy
  • Dietary vitamins and protein supplements
  • Antihistamine medication
  • Anticholesterol medication
  • Cardiac and antihypertensive medication
  • Any medication, as determined by the principal investigator, that is not known or likely to be immunosuppressive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMV-seropositive participants; Participants are randomized to receive 1 of 4 escalating doses of CMVpp65-A*0201 peptide vaccine containing either helper T-lymphocyte (HTL) PADRE peptide or HTL tetanus toxoid peptide. Within each vaccine dose group, two participants are randomized to receive a placebo. Participants receive the vaccine or a placebo subcutaneously (SC) on days 0 and 28 in the absence of unacceptable toxicity.	Biological: CMVpp65-A*0201 peptide vaccine; Vaccine received on either days 0 and 28 or on days 0, 28, and 56 and perhaps day 90
Experimental: CMV-seronegative participants; Participants are randomized to receive 1 of 4 established doses (established in CMV-seropositive participants) of CMVpp65-A*0201 peptide vaccine containing either HTL PADRE peptide or HTL tetanus toxoid peptide. Participants receive the vaccine on days 0, 28, and 56 in the absence of unacceptable toxicity. Participants with a partial or low-level immune response receive one additional booster vaccine on day 90.	Biological: CMVpp65-A*0201 peptide vaccine; Vaccine received on either days 0 and 28 or on days 0, 28, and 56 and perhaps day 90

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and toxicity
Immunologic response
Duration of immunologic response

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Don Diamond, PhD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 1997
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 9, 2008
• First Submitted That Met QC Criteria: July 9, 2008
• First Posted (Estimate): July 10, 2008

Study Record Updates

• Last Update Posted (Estimate): December 21, 2009
• Last Update Submitted That Met QC Criteria: December 18, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: cytomegalovirus infection
• Additional Relevant MeSH Terms: Neoplasms; Precancerous Conditions
• Other Study ID Numbers: CDR0000599675; P01CA030206 (U.S. NIH Grant/Contract); CHNMC-97092