HIV InfectionsPhase 2STALWARTNCT00110812
Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People
A Phase 2 study testing IL-2 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 36 sites in 11 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 267 participants
- Where
- 36 sitesin 11 countries
- Study dates
- Sep 2005to Feb 2011
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
36 sites in 11 countries.
36 sites in 11 countries
United States11 sites
NIH Clinical Ctr., NIAID HIV Clinic CRS
Bethesda, Maryland, 20814-9692
Henry Ford Hosp. CRS
Detroit, Michigan, 48202
Michael E. DeBakey VAMC CRS
Houston, Texas, 77030
Thomas Street Clinic CRS
Houston, Texas, 77030
VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS
Los Angeles, California, 90073
Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
New York, New York, 10037
Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS
Portland, Oregon, 97213
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, 23298
South Texas Veterans Health Care System, Immunosuppression Clinic CRS
San Antonio, Texas, 78229
Lincoln Hosp. & Med. Ctr. CRS
The Bronx, New York, 10451
Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
Washington D.C., District of Columbia, 20422
Australia5 sites
Queensland Health - AIDS Med. Unit CRS
Brisbane, Queensland, 4000
Carlton Clinic CRS
Carlton, Victoria, 3053
St. Vincent's Hospital CRS
Darlinghurst, New South Wales, 2010
Gladstone Road Medical Ctr. CRS
Highgate Hill, Queensland, 4101
Gold Coast Sexual Health Clinic CRS
Miami, Queensland, 4220
Argentina4 sites
Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS
Ciudad de Buenos Aires, Buenos Aires, 1199
Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS
Ciudad de Buenos Aires, Buenos Aires, 1221
Funcei Crs
Ciudad de Buenos Aires, Buenos Aires, C1425-AWK
Caici Crs
Rosario, Provincia de Sante Fe
United Kingdom4 sites
Brighton & Sussex Univ. Hosp. NHS Trust, HIV Research Office CRS
Elm Grove, Brighton
Leicester Royal Infirmary, Dept. of Infection & Tropical Medicine CRS
Leicester
St. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS
London, EC1A 7BE
St. Mary's Hosp. of London, Imperial College School of Medicine CRS
London, W2 1NY
Portugal3 sites
Hospital de Cascais, HDDI, Departamento Medicina Interna CRS
Cascais
Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS
Lisbon
Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS
Lisbon
Thailand3 sites
Chulalongkorn University Hospital CRS
Bangkok, Ratchathewi
Chiang Rai Regional Hosp. INSIGHT CRS
Chiangrai
Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici
Khon Kaen
Italy2 sites
Ospedale San Raffaele S.r.l. CRS
Milan, 20127
Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS
Milan, 20157
Morocco1 site
Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS
Casablanca
About this study
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
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- IL-2
- Keywords
- Treatment Naive, IL-2, rIL-2
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2Drug
Also called Proleukin, Aldeskeukin
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)
| Study group | Role | What they receive |
|---|---|---|
| No IL-2 | No intervention | Participants will receive no aldesleukin or HAART |
| IL-2 without ART | Experimental | 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. Receives: Drug: IL-2 |
| IL-2 with pericycle HAART | Experimental | 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. Receives: Drug: IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in CD4+ T Lymphocyte Count
Change in CD4 count from baseline to week 32.
Measured: Week 32
Secondary outcomes (10)
Discontinuation of IL-2
Patients receiving fewer than 3 cycles of IL-2 by week 32
Measured: week 32
Plasma HIV RNA
change from baseline in HIV-RNA copies/ml (log10)
Measured: At Week 32
Change in CD4 T Lymphocyte Count
change from baseline to month 12 in CD4 T lymphocyte count
Measured: At Month 12
HIV-1 Genotype Changes
Patients who developed mutations associated with antiretroviral drugs.
Measured: after 3rd cycle of IL-2
Fasting Lipid Profile
total fasting cholesterol
Measured: week 32
Disease Progression or Death
occurrence of an opportunistic event (AIDS-defining infection or malignancy) or death
Measured: throughout study, through Feb 28 2009 (median followup of 19 months)
Initiation of Continuous ART
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.
Measured: from randomization through February 28, 2009
Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12
Measured: month 12
Thyroid Stimulating Hormone
Number of participants with thyroid stimulating hormone greater than the upper limit of normal
Measured: week 32
SGOT
Number of participants with aspartate aminotransferase (SGOT) greater than 5 times the upper limit of normal
Measured: week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2005 (estimated)
- Study startSep 2005
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Chiron Corporation
- Responsible party
- Sponsor
- Investigators
- Jorge Tavel, MD, Study chair, National Institute for Allergy and Infectious Diseases, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110812
- Sponsor's protocol ID
- ESPRIT 002
- Other IDs
- 10053
- Acronym
- STALWART
- Status last verified
- Apr 2014
- First submitted
- 13 May 2005
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Anaya JP, Sias JJ. The use of interleukin-2 in human immunodeficiency virus infection. Pharmacotherapy. 2005 Jan;25(1):86-95. doi: 10.1592/phco.25.1.86.55629.
PubMed 15767224de Boer AW, Markowitz N, Lane HC, Saravolatz LD, Koletar SL, Donabedian H, Yoshizawa C, Duliege AM, Fyfe G, Mitsuyasu RT. A randomized controlled trial evaluating the efficacy and safety of intermittent 3-, 4-, and 5-day cycles of intravenous recombinant human interleukin-2 combined with antiretroviral therapy (ART) versus ART alone in HIV-seropositive patients with 100-300 CD4+ T cells. Clin Immunol. 2003 Mar;106(3):188-96. doi: 10.1016/s1521-6616(02)00038-4.
PubMed 12706405Davey RT Jr, Murphy RL, Graziano FM, Boswell SL, Pavia AT, Cancio M, Nadler JP, Chaitt DG, Dewar RL, Sahner DK, Duliege AM, Capra WB, Leong WP, Giedlin MA, Lane HC, Kahn JO. Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. JAMA. 2000 Jul 12;284(2):183-9. doi: 10.1001/jama.284.2.183.
PubMed 10889591Marchetti G, Franzetti F, Gori A. Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap? J Antimicrob Chemother. 2005 Apr;55(4):401-9. doi: 10.1093/jac/dkh557. Epub 2005 Feb 24.
PubMed 15731201Pett SL, Kelleher AD. Cytokine therapies in HIV-1 infection: present and future. Expert Rev Anti Infect Ther. 2003 Jun;1(1):83-96. doi: 10.1586/14787210.1.1.83.
PubMed 15482104Tavel JA; INSIGHT STALWART Study Group; Babiker A, Fox L, Gey D, Lopardo G, Markowitz N, Paton N, Wentworth D, Wyman N. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study. PLoS One. 2010 Feb 23;5(2):e9334. doi: 10.1371/journal.pone.0009334.
PubMed 20186278