Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

NCT ID: NCT00722839

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2012-04-30

Brief 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.

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.

Conditions

Nonneoplastic Condition

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study 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 Type: EXPERIMENTAL

PADRE-CMV fusion peptide vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously

tetanus-CMV fusion peptide vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously

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.

Group Type: EXPERIMENTAL

PADRE-CMV fusion peptide vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously

tetanus-CMV fusion peptide vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously

agatolimod sodium

Intervention Type: DRUG

Given subcutaneously

Interventions

PADRE-CMV fusion peptide vaccine

Given subcutaneously

Intervention Type: BIOLOGICAL

tetanus-CMV fusion peptide vaccine

Given subcutaneously

Intervention Type: BIOLOGICAL

agatolimod sodium

Given subcutaneously

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John A. Zaia, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22402037 (View on PubMed)

Other Identifiers

R01CA077544

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-03121

Identifier Type: -

Identifier Source: secondary_id

CDR0000599724

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2010-01227

Identifier Type: REGISTRY

Identifier Source: secondary_id

City of Hope 03121

Identifier Type: -

Identifier Source: org_study_id