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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00110812




Registration number
NCT00110812
Ethics application status
Date submitted
13/05/2005
Date registered
13/05/2005
Date last updated
7/04/2014

Titles & IDs
Public title
Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People
Scientific 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
Secondary ID [1] 0 0
10053
Secondary ID [2] 0 0
ESPRIT 002
Universal Trial Number (UTN)
Trial acronym
STALWART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IL-2

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.

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.


Treatment: Drugs: 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)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in CD4+ T Lymphocyte Count - Change in CD4 count from baseline to week 32.
Timepoint [1] 0 0
Week 32
Secondary outcome [1] 0 0
Discontinuation of IL-2 - Patients receiving fewer than 3 cycles of IL-2 by week 32
Timepoint [1] 0 0
week 32
Secondary outcome [2] 0 0
Plasma HIV RNA - change from baseline in HIV-RNA copies/ml (log10)
Timepoint [2] 0 0
At Week 32
Secondary outcome [3] 0 0
Change in CD4 T Lymphocyte Count - change from baseline to month 12 in CD4 T lymphocyte count
Timepoint [3] 0 0
At Month 12
Secondary outcome [4] 0 0
HIV-1 Genotype Changes - Patients who developed mutations associated with antiretroviral drugs.
Timepoint [4] 0 0
after 3rd cycle of IL-2
Secondary outcome [5] 0 0
Fasting Lipid Profile - total fasting cholesterol
Timepoint [5] 0 0
week 32
Secondary outcome [6] 0 0
Disease Progression or Death - occurrence of an opportunistic event (AIDS-defining infection or malignancy) or death
Timepoint [6] 0 0
throughout study, through Feb 28 2009 (median followup of 19 months)
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
from randomization through February 28, 2009
Secondary outcome [8] 0 0
Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12
Timepoint [8] 0 0
month 12
Secondary outcome [9] 0 0
Thyroid Stimulating Hormone - Number of participants with thyroid stimulating hormone greater than the upper limit of normal
Timepoint [9] 0 0
week 32
Secondary outcome [10] 0 0
SGOT - Number of participants with aspartate aminotransferase (SGOT) greater than 5 times the upper limit of normal
Timepoint [10] 0 0
week 32

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital CRS - Darlinghurst
Recruitment hospital [2] 0 0
Queensland Health - AIDS Med. Unit CRS - Brisbane
Recruitment hospital [3] 0 0
Gladstone Road Medical Ctr. CRS - Highgate Hill
Recruitment hospital [4] 0 0
Gold Coast Sexual Health Clinic CRS - Miami
Recruitment hospital [5] 0 0
Carlton Clinic CRS - Carlton
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
4000 - Brisbane
Recruitment postcode(s) [3] 0 0
4101 - Highgate Hill
Recruitment postcode(s) [4] 0 0
4220 - Miami
Recruitment postcode(s) [5] 0 0
3053 - Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Provincia de Sante Fe
Country [11] 0 0
Chile
State/province [11] 0 0
Santiago
Country [12] 0 0
Italy
State/province [12] 0 0
Milano
Country [13] 0 0
Morocco
State/province [13] 0 0
Casablanca
Country [14] 0 0
Poland
State/province [14] 0 0
Warsaw
Country [15] 0 0
Portugal
State/province [15] 0 0
Cascais
Country [16] 0 0
Portugal
State/province [16] 0 0
Lisboa
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Thailand
State/province [18] 0 0
Ratchathewi
Country [19] 0 0
Thailand
State/province [19] 0 0
Chiangrai
Country [20] 0 0
Thailand
State/province [20] 0 0
Khon Kaen
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Brighton
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Leicester
Country [23] 0 0
United Kingdom
State/province [23] 0 0
London

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Chiron Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.

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.
Trial website
https://clinicaltrials.gov/show/NCT00110812
Trial related presentations / publications
Anaya JP, Sias JJ. The use of interleukin-2 in human immunodeficiency virus infection. Pharmacotherapy. 2005 Jan;25(1):86-95. Review.
de 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.
Davey 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.
Marchetti 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. Epub 2005 Feb 24. Review.
Pett SL, Kelleher AD. Cytokine therapies in HIV-1 infection: present and future. Expert Rev Anti Infect Ther. 2003 Jun;1(1):83-96. Review.
Public notes

Contacts
Principal investigator
Name 0 0
Jorge Tavel, MD
Address 0 0
National Institute for Allergy and Infectious Diseases, National Institutes of Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications