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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: IL-2
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 267
Study Start Date: September 2005
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00110812

  Hide Study Locations
Locations
United States, California
VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS
Los Angeles, California, United States, 90073
United States, District of Columbia
Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
Washington, District of Columbia, United States, 20422
United States, Maryland
NIH Clinical Ctr., NIAID HIV Clinic CRS
Bethesda, Maryland, United States, 20814-9692
United States, Michigan
Henry Ford Hosp. CRS
Detroit, Michigan, United States, 48202
United States, New York
Lincoln Hosp. & Med. Ctr. CRS
Bronx, New York, United States, 10451
Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
New York, New York, United States, 10037
United States, Oregon
Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS
Portland, Oregon, United States, 97213
United States, Texas
Thomas Street Clinic CRS
Houston, Texas, United States, 77030
Michael E. DeBakey VAMC CRS
Houston, Texas, United States, 77030
South Texas Veterans Health Care System, Immunosuppression Clinic CRS
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, United States, 23298
Argentina
Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS
Ciudad de Buenos Aires, Buenos Aires, Argentina, 1199
Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS
Ciudad de Buenos Aires, Buenos Aires, Argentina, 1221
Funcei Crs
Ciudad de Buenos Aires, Buenos Aires, Argentina, C1425-AWK
Caici Crs
Rosario, Provincia de Sante Fe, Argentina
Australia, New South Wales
St. Vincent's Hospital CRS
Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
Queensland Health - AIDS Med. Unit CRS
Brisbane, Queensland, Australia, 4000
Gladstone Road Medical Ctr. CRS
Highgate Hill, Queensland, Australia, 4101
Gold Coast Sexual Health Clinic CRS
Miami, Queensland, Australia, 4220
Australia, Victoria
Carlton Clinic CRS
Carlton, Victoria, Australia, 3053
Chile
Fundacion Arriaran CRS
Santiago, Chile
Italy
Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS
Milano, Italy, 20157
Ospedale San Raffaele S.r.l. CRS
Milano, Italy, 20127
Morocco
Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS
Casablanca, Morocco
Poland
Wojewodzki Szpital Zakazny CRS
Warsaw, Poland
Portugal
Hospital de Cascais, HDDI, Departamento Medicina Interna CRS
Cascais, Portugal
Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS
Lisboa, Portugal
Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS
Lisboa, Portugal
Spain
Hosp. Clinico de Barcelona CRS
Barcelona, Spain
Thailand
Chulalongkorn University Hospital CRS
Bangkok, Ratchathewi, Thailand
Chiang Rai Regional Hosp. INSIGHT CRS
Chiangrai, Thailand
Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici
Khon Kaen, Thailand
United Kingdom
Brighton & Sussex Univ. Hosp. NHS Trust, HIV Research Office CRS
Elm Grove, Brighton, United Kingdom
Leicester Royal Infirmary, Dept. of Infection & Tropical Medicine CRS
Leicester, United Kingdom
St. Mary's Hosp. of London, Imperial College School of Medicine CRS
London, United Kingdom, W2 1NY
St. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS
London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Chiron Corporation
Investigators
Study Chair: Jorge Tavel, MD National Institute for Allergy and Infectious Diseases, National Institutes of Health
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00110812     History of Changes
Obsolete Identifiers: NCT00106730
Other Study ID Numbers: ESPRIT 002, 10053
Study First Received: May 13, 2005
Results First Received: December 12, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
IL-2
rIL-2

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protease Inhibitors
Reverse Transcriptase Inhibitors
Aldesleukin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antineoplastic Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 16, 2014