A Phase I Dose Escalation Study of Peptide Vaccines With Activity Against Human Cytomegalovirus
18 Years
55 Years
Both
Nonneoplastic Condition
Trial Information
A Phase I Dose Escalation Study of Peptide Vaccines With Activity Against Human Cytomegalovirus
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Successful completion of a series of 4 injections (at weeks 0, 3, 6, and 9) without dose-limiting toxicity
Outcome Time Frame:
3 weeks after the final vaccine dose
Safety Issue:
Yes
Principal Investigator
John A. Zaia, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
City of Hope 03121
NCT ID:
NCT00722839
Start Date:
December 2006
Completion Date:
April 2012
Related Keywords:
- Nonneoplastic Condition
- cytomegalovirus infection
Name | Location |
|---|---|
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
