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

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00110578
First received: May 10, 2005
Last updated: August 7, 2008
Last verified: July 2007
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: Stanley Riddell, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided by National Institute of Allergy and Infectious Diseases (NIAID)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00110578     History of Changes
Other Study ID Numbers: 5U01AI054334-02, AI54334
Study First Received: May 10, 2005
Last Updated: August 7, 2008
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014