Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

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

RATIONALE: Vaccines made from peptides may help the body build an immune response to kill cytomegalovirus.

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

Study Overview

• Status: Completed
• Conditions: Nonneoplastic Condition
• Intervention / Treatment: Biological: PADRE-CMV fusion peptide vaccine; Biological: tetanus-CMV fusion peptide vaccine; Drug: agatolimod sodium

Detailed Description

OBJECTIVES:

Primary

• To establish whether 3 vaccine dose levels of PADRE-CMV and tetanus-CMV fusion peptide vaccines are safe and well tolerated in healthy cytomegalovirus (CMV)-seropositive or -seronegative participants.
• To establish safe dose levels for the PADRE-CMV and tetanus-CMV fusion peptide vaccines in combination with PF 03512676 DNA in these participants.

Secondary

• To provide preliminary evidence of enhanced cellular immunity to CMV at levels of T cells that would support potential feasibility if such cells were to be transferred from the donor to recipients of hematopoietic stem cell transplantation (HSCT) in amounts consistent with protection against disease.
• To determine whether a reduced dose of peptide vaccine can be immunogenic in combination with PF 03512676 DNA.
• To confer CMV-specific cytotoxic T-lymphocyte (CTL) function to CMV-negative participants.
• To determine the duration of immune enhancement of CMV-specific CTL function up to 12 months following immunization of healthy participants.

OUTLINE: This is a dose-escalation study of PADRE-CMV and tetanus-CMV fusion peptide vaccines. Participants are stratified according to cytomegalovirus (CMV) serum status (positive vs negative). Participants are assigned to 1 of 2 groups.

• Group A: Participants receive either PADRE-CMV fusion peptide vaccine or tetanus-CMV fusion peptide vaccine subcutaneously (SC) on days 1, 21, 42, and 63 in the absence of unacceptable toxicity.
• Group B: Participants receive either PADRE-CMV fusion peptide vaccine in CpG 7909 adjuvant SC or tetanus-CMV fusion peptide vaccine in CpG 7909 adjuvant SC on days 1, 21, 42, and 63 in the absence of unacceptable toxicity.

Participants are contacted by telephone every 3-7 days after immunization. Participants also complete a notebook on any health-related event for 14 days after each immunization.

Participants undergo blood sample collection at baseline and periodically during study for immunologic laboratory studies, including flow cytometry, by HLA-A2-CMV-tetramer, CMV-specific intracellular cytokine, CMV-specific CD107 degranulation, lymphoproliferation, and chromium release assays.

After completion of study therapy, participants are followed for up to 1 year.

• Study Type: Interventional
• Enrollment (Actual): 68
• 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 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Cytomegalovirus (CMV) seropositivity or seronegativity
• HLA A*0201 positive OR positive tetramer-binding using CMV peptide 495-503 with HLA A2 subtypes other than HLA A*0201
• A2-CMV-Tet cells ≤ 10^8/L

PATIENT CHARACTERISTICS:

• Platelet count within 1.5 times upper level of normal (ULN)

• The following blood and chemistry studies must be normal:

  • Sodium
  • Potassium
  • Chloride
  • Carbon dioxide
  • Glucose
  • BUN
  • Creatinine
  • Uric acid
  • WBC
  • Hemoglobin
  • Hematocrit

• The following studies must be ≤ ULN:

  • Albumin
  • Alkaline phosphatase
  • AST and ALT
  • Lactic dehydrogenase
  • Total bilirubin
• Hepatitis B virus surface antigen negative
• Hepatitis C virus seronegative
• No diagnosis that is associated with immunodeficiency (e.g., HIV)
• No active infection that requires treatment
• No known cardiac disease including hypertension and/or high cholesterol
• No serious abnormalities by EKG (in participants ≥ 50 years of age)
• Not pregnant
• Negative pregnancy test
• Fertile participants must use effective contraception during study and for 6 weeks after the fourth and last dose of vaccine
• No history of allergic reaction to tetanus toxoid

• No history of any of the following:

  • Cancer other than basal cell carcinoma of the skin
  • Depression
  • Allergic diathesis, as defined by a history of asthma
  • Anaphylaxis
  • Generalized urticaria or daily use of antihistamines
  • Episodic (more than once in the past 3 months) inhalational medications including steroidal agents
  • Non-steroidal agents or cromolyn sodium
  • Frequent migraines, defined as 3 or more episodes in the past year
• No prior or concurrent infectious condition

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior participation in a CMV immunotherapy trial
• More than 30 days since prior live vaccine
• More than 2 weeks since prior inactivated vaccine

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

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

• No surgery in the past 6 months that required general anesthesia

  • Minor procedures (e.g., dental surgery or superficial diagnostics biopsies) allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Participants receive either PADRE-CMV fusion peptide vaccine or tetanus-CMV fusion peptide vaccine subcutaneously (SC) on days 1, 21, 42, and 63 in the absence of unacceptable toxicity.	Biological: PADRE-CMV fusion peptide vaccine; Given subcutaneously; Biological: tetanus-CMV fusion peptide vaccine; Given subcutaneously
Experimental: Group B; Participants receive either PADRE-CMV fusion peptide vaccine in CpG 7909 adjuvant SC or tetanus-CMV fusion peptide vaccine in CpG 7909 adjuvant SC on days 1, 21, 42, and 63 in the absence of unacceptable toxicity.	Biological: PADRE-CMV fusion peptide vaccine; Given subcutaneously; Biological: tetanus-CMV fusion peptide vaccine; Given subcutaneously; Drug: agatolimod sodium; Given subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Successful completion of a series of 4 injections (at weeks 0, 3, 6, and 9) without dose-limiting toxicity	3 weeks after the final vaccine dose
Maximum tolerated dose of each vaccine with or without adjuvant CpG 7909	1 year after the final vaccine dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of CMV-positive and CMV-specific CD8+ T cells/L	1 year after final vaccine dose

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John A. Zaia, MD, City of Hope Comprehensive Cancer Center

Publications and helpful links

General Publications

• La Rosa C, Longmate J, Lacey SF, Kaltcheva T, Sharan R, Marsano D, Kwon P, Drake J, Williams B, Denison S, Broyer S, Couture L, Nakamura R, Dadwal S, Kelsey MI, Krieg AM, Diamond DJ, Zaia JA. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant. J Infect Dis. 2012 Apr 15;205(8):1294-304. doi: 10.1093/infdis/jis107. Epub 2012 Mar 7. Erratum In: J Infect Dis. 2013 Sep;208(6):1038. Dadwal, Sanjeet [added].

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 25, 2008
• First Submitted That Met QC Criteria: July 25, 2008
• First Posted (Estimate): July 28, 2008

Study Record Updates

• Last Update Posted (Estimate): June 25, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: cytomegalovirus infection
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: City of Hope 03121; P30CA033572 (U.S. NIH Grant/Contract); R01CA077544 (U.S. NIH Grant/Contract); CHNMC-03121; CDR0000599724 (Registry Identifier: NCI PDQ); NCI-2010-01227 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No