Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

Nonneoplastic Condition Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00722839
• Other study ID #: City of Hope 03121
• Secondary ID: R01CA077544P30CA
• Status: Completed
• Phase: Phase 1
• First received: July 25, 2008
• Last updated: June 21, 2012
• Start date: December 2006
• Est. completion date: April 2012

Study information

• Verified date: June 2012
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nonneoplastic Condition

Intervention

Biological:
• PADRE-CMV fusion peptide vaccine
Given subcutaneously
• tetanus-CMV fusion peptide vaccine
Given subcutaneously

Drug:
• agatolimod sodium
Given subcutaneously

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Maximum tolerated dose of each vaccine with or without adjuvant CpG 7909		1 year after the final vaccine dose	Yes
Secondary	Number of CMV-positive and CMV-specific CD8+ T cells/L		1 year after final vaccine dose	No