Safety and Effectiveness of Immunotherapy With Autologous HIV-Specific CD8 Cells in HIV Infected Adults - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00110578

Purpose

Effective, suppressive treatment for HIV infected patients can be a major challenge because HIV progressively destroys their immune systems. CD8 cells isolated from a patient's blood and grown in large numbers in the laboratory may increase a patient's immune system response to HIV. The purpose of this study is to determine if CD8 cells will provide effective antiviral activity against HIV when transplanted back in large numbers into HIV infected patients.

Study hypothesis: There are specific cells in the immune system that recognize and can kill HIV-infected cells.

Condition	Intervention	Phase
HIV Infections	Procedure: Adoptive transfer of HIV-specific CD8+ T cells Drug: Aldesleukin	Phase I

MedlinePlus related topics: AIDS

Drug Information available for: Aldesleukin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Safety and Antiviral Efficacy of Cellular Adoptive Immunotherapy With Autologous CD8+ HIV-Specific Cytotoxic T Cells Combined With Interleukin-2 For HIV Seropositive Individuals

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

To determine the safety of administering CD8+ HIV-specific CTL clones followed by subcutaneous IL-2 (Proleukin, Chiron) daily for up to 21 days
To identify a regimen of IL-2 that will improve the in vivo persistence and function of adoptively transferred CD8+ HIV-specific CTL

Secondary Outcome Measures:

To determine whether the administration of IL-2 prolongs the antiviral activity of transferred CD8+ HIV-specific CTL
To determine if IL-2 promotes the accumulation of adoptively transferred CD8+ HIV-specific CTL in lymph nodes

Estimated Enrollment:	24
Study Start Date:	September 1998
Estimated Study Completion Date:	April 2005

Detailed Description:

The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells.

However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo.

Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of antiviral activity without severe toxicity.

This study will last 18 months. CD8 cells will be isolated from the blood of HIV infected patients; the cells will be allowed to multiply in the laboratory, and patients will receive back their CD8 cells. Patients will receive up to 3 infusions of self CD8 cells. On Day 0, patients will receive their first infusion of CD8 cells. On Day 7, patients will receive their second infusion of CD8 cells; this infusion will be followed by 14 days of aldesleukin administered daily by injection under the skin. Patients with less than a Grade 2 toxicity will receive a third infusion of CD8 cells; this infusion will be followed by 21 days of aldesleukin.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for All Participants:

HIV infected
CD4 count greater than 200 cells/mm3 at study entry
Absolute neutrophil count greater than 1000 cells/mm3
Willing to take Pneumocystis prophylaxis, if indicated
Willing to comply with study requirements
Willing to forgo other experimental therapy during the 26-week study period
Willing to use acceptable forms of contraception

Inclusion Criteria for Treatment-Experienced Participants:

Currently receiving treatment with an FDA-approved or expanded access antiretroviral agent (or combinations thereof) at a stable dose for at least 24 weeks prior to study entry

Inclusion Criteria for Treatment-Naive Participants:

Have not received antiretroviral therapy for 6 months prior to study entry

Exclusion Criteria:

Treatment with other immunomodulatory therapies (interferon, HIV vaccines, intravenous immunoglobulin), pentoxifylline, cancer chemotherapy, radiation therapy, or other investigational agents
Past or present infection with mycobacterium avium complex, toxoplasmosis, cryptococcus, or cytomegalovirus (including retinitis)
Active opportunistic infection at study entry or serious systemic infection requiring chronic maintenance or suppressive therapy
Lymphoma, symptomatic visceral Kaposi's sarcoma, or any malignancy expected to require systemic therapy
Serious psychological or emotional disorder that would affect ability to comply with study requirements or that would be exacerbated by protocol participation
Alcohol or drug use, abuse, or dependence that, in the opinion of the investigator, would interfere with the study
Estimated life expectancy of less than 4 months
Abnormal neurocognitive examination
Significant abnormality on electrocardiogram or chest radiograph
Inability to generate CD8+ HIV-specific cytotoxic T cell clones
Previously treated in FHCRC Protocol #827.1
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110578

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
University of Washington (UW)
Seattle, Washington, United States, 98122

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

Stanley Riddell, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Click here for more information on aldesleukin This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	5U01AI054334-02, AI54334
Study First Received:	May 10, 2005
Last Updated:	August 7, 2008
ClinicalTrials.gov Identifier:	NCT00110578 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Naive
Treatment Experienced

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Aldesleukin
Anti-Retroviral Agents
Interleukin-2

HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Antiviral Agents
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Antineoplastic Agents
Acquired Immunodeficiency Syndrome
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases
Aldesleukin
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on May 07, 2009