Protocol Number: 06-C-0211

Title:

A Pilot Study to Investigate the Safety and Immunogenicity of a Peptide Vaccine for HIV Infected HLA-A2 Individuals Designed to Impede the Development of Antiretroviral Resistance

Number:

06-C-0211

Summary:

This study will evaluate the safety of a peptide vaccine in otherwise healthy patients who have the human immunodeficiency virus (HIV) and look at its effects on viral load, or amount of virus in the blood. HIV infection is a chronic disease that destroys the immune system, resulting in AIDS and death. If not treated, the infection lowers the count of helper cells, CD4+ T, which fight infections.

Patients ages 18 and older with HIV infection who are not pregnant or breastfeeding and who have not had a severe infection other than HIV within 6 months of study entry may be eligible for this study. This study involves immunogenicity, the ability of a vaccine to enter the immune system to create a response. Patients will receive a peptide, or small piece of a larger protein, called E1M184V. It will be mixed with Montanide ISA-51, to assist the immune system in creating a good response to the peptide. An additional help will come from an injection of a chemical called GM-CSF, or sargramostim . It will be given separately on the day of vaccination and again daily for the following 3 days. Researchers will do blood tests to monitor for safety, and patients will keep a diary of side effects experienced. Before vaccination begins, patients who use the drug lamivudine (3TC) will discontinue it. Patients also may be asked to stop taking other drugs that interfere with the vaccination.

The vaccination phase of the study goes from weeks 0 to 16, with vaccination given every 4 weeks under the skin in the upper arm, thigh, or lower abdomen. Injection sites will be changed each session to avoid repeated dosing at one site. One injection of the vaccine will be given in each 4-week cycle, but there will be four daily injections of sargramostim. At the beginning of each vaccine cycle, patients will undergo a physical exam and donate blood samples to be used in specialized tests to monitor the immune system's ability to create a response. The follow-up phase goes from weeks 20 through 52 or through week 104, depending on whether patients choose to go on to lamivudine after the vaccine phase.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Age greater than or equal to 18 years.

2. HIV-1 infection confirmed by Western Blot and ELISA.

3. HLA A2 confirmed by PCR-SSP Method .

4. CD4 T Cell count greater than or equal to 300 cells/mm(3) within two weeks of enrollment.

5. Patients must be on a stable regimen of highly active antiretroviral therapy that does not include lamivudine or emtracitabine for at least one month prior to enrollment. Patients on a HAART including lamivudine or emtracitabine, for which there is a medically appropriate regimen that does not include lamivudine or emtracitabine, will be eligible if they are willing to change antiretrovirals as described in Modifications of HAART section 3.5.2

6. Patients must have a viral load less than 50 copies/ml for one month prior to enrollment.

7. ECOG performance status less than or equal to 1.

8. Life expectancy greater than or equal to 6 months.

9. The following hematologic parameters:

-Hemoglobin greater than or equal to 9 g/dl

-WBC greater than or equal to 1000/mm3

-ANC greater than or equal to 750/mm3

-Platelets greater than or equal to 75,000/mm3

10. PT and PTT less than or equal to 120% of control unless lupus anticoagulant is detected.

11. The following hepatic parameters:

-Bilirubin less than or equal to 1.5 X ULN unless the patient is receiving protease inhibitor therapy or has Gilbert's syndrome; in this case total bilirubin less than or equal to 7.5 mg/dl with direct fraction less than or equal to 0.7citabine mg/dl.

-AST/ALT less than or equal to 2.5 times the upper limit of normal.

12. Serum creatinine less than or equal to 1.5 mg/dL or measured creatinine clearance greater than or equal to 60 mL/min.

13. Ability and willingness to give informed consent.

EXCLUSION CRITERIA:

1. Patients with current Hepatitis B surface antigen or on lamivudine or emtracitabine with a prior history of Hepatitis B surface antigen will be ineligible. This is because lamivudine or emtracitabine is effective in suppressing Hepatitis B replication and minimizing the clinical sequelae of infection. Patients treated for Hepatitis B with tenofovir who are currently surface antigen negative and not on lamivudine or emtracitabine will be eligible for the study.

2. Systemic corticosteroids within 3 weeks.

3. Pregnancy (because of unknown effects of cytokine administration on fetal formation).

4. Breast feeding (because of unknown potential for adverse infant developmental consequences).

5. Evidence of a severe or life-threatening infection other than HIV within 6 months of entry onto the study, or opportunistic infections requiring systemic therapy within 1 month.

6. Other active malignancy, except for basal cell carcinoma.

7. Known hypersensitivity to Montanide ISA 51 VG, E1M184V, or GM-CSF/sargramostim.

8. Previous vaccination with a vaccine that includes all or part of the reverse transcriptase of HIV-1.

9. Patients with any other abnormality that would be scored as a grade 3 toxicity or higher, except asymptomatic:

-Hyperuricemia of grade 4 (asymptomatic or without physiologic consequences)

-Elevation of LDH grade 3

-Elevation of CPK grade 3

-Hypohosphatemia greater than or equal to grade 3 (if patient is on tenofovir)

-Elevation of alkaline phosphate of grade 3

Patients with hyperamylasemia of greater than or equal to grade 3 will be eligible if they have either:

-Macroamylasemia, or

-Lipase less than or equal to 2X the upper limit of normal

-Lymphopenia grade 3

10. Patients taking other investigational drugs are excluded.

11. Any condition that, in the opinion of the Principal Investigator or Study Chairperson, would preclude the inclusion of a patient onto this research study.

Special Instructions:

Currently Not Provided

Keywords:

AIDS

Antiviral

Adjuvant

Antiretroviral Therapy

Vaccination

Recruitment Keyword(s):

Melanoma

Malignant Melanoma

Renal Cell Cancer

Condition(s):

HIV Resistance

Investigational Drug(s):

Montanide ISA-51VG

E1M184V Peptide

Investigational Device(s):

None

Intervention(s):

Drug: Montanide ISA-51VG

Drug: E1M184V Peptide

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Levin SA, Grenfell B, Hastings A, Perelson AS. Mathematical and computational challenges in population biology and ecosystems science. Science. 1997 Jan 17;275(5298):334-43. Review.

Hogg RS, O'Shaughnessy MV, Gataric N, Yip B, Craib K, Schechter MT, Montaner JS. Decline in deaths from AIDS due to new antiretrovirals. Lancet. 1997 May 3;349(9061):1294. No abstract available.

Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 09/15/2008