Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Nonneoplastic Condition

Intervention / Treatment
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* Biological: PADRE-CMV fusion peptide vaccine
* Biological: tetanus-CMV fusion peptide vaccine
* Drug: agatolimod sodium


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>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<br>* Given subcutaneously<br>Biological: tetanus-CMV fusion peptide vaccine<br>* Given subcutaneously<br>|
| Experimental: Group B<br>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<br>* Given subcutaneously<br>Biological: tetanus-CMV fusion peptide vaccine<br>* Given subcutaneously<br>Drug: agatolimod sodium<br>* Given subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cytomegalovirus infection