Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People (STALWART)

This study has been completed.
Sponsor:
Collaborator:
Chiron Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00110812
First received: May 13, 2005
Last updated: April 7, 2014
Last verified: April 2014

May 13, 2005
April 7, 2014
September 2005
February 2011   (final data collection date for primary outcome measure)
Mean Change in CD4+ T Lymphocyte Count [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
Change in CD4 count from baseline to week 32.
Mean change in CD4+ T lymphocyte count from baseline (average of two pre-randomization counts) to Week 32 in the three study groups
Complete list of historical versions of study NCT00110812 on ClinicalTrials.gov Archive Site
  • Discontinuation of IL-2 [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Patients receiving fewer than 3 cycles of IL-2 by week 32
  • Plasma HIV RNA [ Time Frame: At Week 32 ] [ Designated as safety issue: No ]
    change from baseline in HIV-RNA copies/ml (log10)
  • Change in CD4 T Lymphocyte Count [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    change from baseline to month 12 in CD4 T lymphocyte count
  • HIV-1 Genotype Changes [ Time Frame: after 3rd cycle of IL-2 ] [ Designated as safety issue: No ]
    Patients who developed mutations associated with antiretroviral drugs.
  • Fasting Lipid Profile [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    total fasting cholesterol
  • Disease Progression or Death [ Time Frame: throughout study, through Feb 28 2009 (median followup of 19 months) ] [ Designated as safety issue: No ]
    occurrence of an opportunistic event (AIDS-defining infection or malignancy) or death
  • Initiation of Continuous ART [ Time Frame: from randomization through February 28, 2009 ] [ Designated as safety issue: No ]
    While patients were not taking ART at baseline or while undergoing IL-2 cycles (other than use of pericycle ART in one of the three groups), some chose to start an ART regimen during the study.
  • Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12 [ Time Frame: month 12 ] [ Designated as safety issue: No ]
  • Thyroid Stimulating Hormone [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Number of participants with thyroid stimulating hormone greater than the upper limit of normal
  • SGOT [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Number of participants with aspartate aminotransferase (SGOT) greater than 5 times the upper limit of normal
  • Grade 3 and 4 events
  • therapy modification as defined by the protocol
  • plasma HIV RNA evaluated at Week 32 and Month 12
  • CD4 T lymphocyte count evaluated at Month 12
  • HIV-1 genotype changes
  • fasting lipid profile and thyroid stimulating hormone and hepatic transaminase levels
Not Provided
Not Provided
 
Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People
STALWART: A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 With and Without Concomitant Antiretroviral Therapy in Patients With HIV-1 Infection and CD4+ Cell Counts of 300 Cells/mm3 or More

The purpose of this study is to determine the effect of short cycles of recombinant interleukin-2 (also known as rIL-2 or aldesleukin) given with or without anti-HIV drugs in HIV infected patients. The effects will be compared with a study group that receives no IL-2 or antiretroviral therapy.

Study hypothesis: Intermittent aldesleukin, when given without antiretroviral therapy to patients with early HIV infection, will produce no change in HIV viral load and increases in CD4+ T lymphocyte counts comparable to aldesleukin administered with antiretrovirals.

Highly active antiretroviral therapy (HAART) has dramatically improved prognosis and lowered morbidity and mortality rates for HIV infected patients. However, significant drug toxicities, difficulties with patient compliance to HAART regimens, and development of drug resistance highlight the need for less toxic, immune-based strategies. Aldesleukin is a synthetic protein that can increase CD4 counts; it is currently approved by the Food and Drug Administration (FDA) for use in patients with metastatic melanoma and renal cell carcinoma. Previous studies of aldesleukin in HIV infected patients indicated that increased CD4 counts can persist for years after aldesleukin administration, and aldesleukin given with HAART may also lead to significant lowering of viral load. This study will examine the immunologic effects of intermittent cycles of aldesleukin administered with and without HAART as compared to no therapy in HIV infected patients.

This study will last approximately 31 months. Participants will be randomly assigned to one of three groups at study entry. Group A will receive no aldesleukin or HAART. Group B will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Group C will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group C participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). HAART will not be provided by the study. Some Group B and C participants may take part in additional cycles of aldesleukin if they meet certain study criteria.

All participants in this study will have at least 8 study visits; these visits will occur at study entry and Weeks 4, 8, 12, 16, 20, 24, and 32. Blood collection will occur at all visits and will include tests for CD4 count and viral load. Groups B and C will have additional blood collection within 4 days prior to the start of each aldesleukin cycle. On the last day of each aldesleukin cycle, Groups B and C will be assessed for toxicities, adverse events, and adherence to the aldesleukin daily injections; they will also have another blood collection. Group C participants will have an additional blood collection for HIV genotyping after they have completed their third aldesleukin cycle. Extended follow-up visits will occur approximately every 4 months for an additional two years. Blood collection will occur at these visits and will include tests for CD4 count, viral load, and other laboratory tests.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
Drug: IL-2
7.5 MIU injected intramuscularly; one arm uses Proleukin together with HAART of choice (protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors)
Other Name: Proleukin, Aldeskeukin
  • No Intervention: No IL-2
    Participants will receive no aldesleukin or HAART
  • Experimental: IL-2 without ART
    Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Some Group 2 participants may take part in additional cycles of aldesleukin if they meet certain study criteria.
    Intervention: Drug: IL-2
  • Experimental: IL-2 with pericycle HAART
    Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group 3 participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). Some Group 3 participants may take part in additional cycles of aldesleukin if they meet certain study criteria. HAART is not supplied by the study, and choice of drugs is left to the participant and physician. The HAART regimen should include at least one protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors.
    Intervention: Drug: IL-2

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
267
February 2011
February 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV infected
  • CD4 count of 300 cells/mm3 or more
  • Access to a HAART regimen consisting of 1 or more protease inhibitors (PIs) and 2 or more nucleoside or nucleotide reverse transcriptase inhibitors

Exclusion Criteria:

  • Prior use of aldesleukin
  • Approved or experimental antiretroviral drug (including hydroxyurea) within 1 year prior to study entry
  • Evidence of virologic failure on a PI- or nonnucleoside-based HAART regimen
  • Any current indication for continuous HAART, in the opinion of the investigator
  • Any contraindication to HAART, in the opinion of the investigator
  • Systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days of randomization
  • Approved or experimental agents with clinically significant immunomodulatory effects within 8 weeks prior to randomization
  • History of any AIDS-defining illness or certain other diseases. More information on this criterion can be found in the protocol.
  • Concurrent cancer requiring cytotoxic therapy
  • Any central nervous system (CNS) abnormality requiring ongoing treatment with antiseizure medication
  • Current or prior autoimmune or inflammatory diseases, including inflammatory bowel disease, psoriasis, optic neuritis, or any other autoimmune or inflammatory diseases with potentially life-threatening complications
  • Significant heart, lung, kidney, liver, gastrointestinal, CNS, or psychiatric disease OR illicit substance use or abuse that, in the opinion of the investigator, would interfere with the study
  • Pregnancy or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Chile,   Italy,   Morocco,   Poland,   Portugal,   Spain,   Thailand,   United Kingdom
 
NCT00110812
ESPRIT 002, 10053
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Chiron Corporation
Study Chair: Jorge Tavel, MD National Institute for Allergy and Infectious Diseases, National Institutes of Health
National Institute of Allergy and Infectious Diseases (NIAID)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP