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

HIV Infections Clinical Trial

— STALWART  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110812
• Other study ID #: ESPRIT 002
• Secondary ID: 10053
• Status: Completed
• Phase: Phase 2
• Start date: September 2005
• Est. completion date: February 2011

Study information

• Verified date: April 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Other known NCT identifiers

• NCT00106730

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections
• Infections

Intervention

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)

Locations

Country	Name	City	State
Argentina	Funcei Crs	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS	Ciudad de Buenos Aires	Buenos Aires
Argentina	Caici Crs	Rosario	Provincia De Sante Fe
Australia	Queensland Health - AIDS Med. Unit CRS	Brisbane	Queensland
Australia	Carlton Clinic CRS	Carlton	Victoria
Australia	St. Vincent's Hospital CRS	Darlinghurst	New South Wales
Australia	Gladstone Road Medical Ctr. CRS	Highgate Hill	Queensland
Australia	Gold Coast Sexual Health Clinic CRS	Miami	Queensland
Chile	Fundacion Arriaran CRS	Santiago
Italy	Ospedale San Raffaele S.r.l. CRS	Milano
Italy	Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS	Milano
Morocco	Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS	Casablanca
Poland	Wojewodzki Szpital Zakazny CRS	Warsaw
Portugal	Hospital de Cascais, HDDI, Departamento Medicina Interna CRS	Cascais
Portugal	Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS	Lisboa
Portugal	Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS	Lisboa
Spain	Hosp. Clinico de Barcelona CRS	Barcelona
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
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. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS	London
United Kingdom	St. Mary's Hosp. of London, Imperial College School of Medicine CRS	London
United States	NIH Clinical Ctr., NIAID HIV Clinic CRS	Bethesda	Maryland
United States	Lincoln Hosp. & Med. Ctr. CRS	Bronx	New York
United States	Henry Ford Hosp. CRS	Detroit	Michigan
United States	Michael E. DeBakey VAMC CRS	Houston	Texas
United States	Thomas Street Clinic CRS	Houston	Texas
United States	VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS	Los Angeles	California
United States	Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)	New York	New York
United States	Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS	Portland	Oregon
United States	Virginia Commonwealth Univ. Medical Ctr. CRS	Richmond	Virginia
United States	South Texas Veterans Health Care System, Immunosuppression Clinic CRS	San Antonio	Texas
United States	Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Chiron Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Chile,  Italy,  Morocco,  Poland,  Portugal,  Spain,  Thailand,  United Kingdom, 

References & Publications (5)

Anaya JP, Sias JJ. The use of interleukin-2 in human immunodeficiency virus infection. Pharmacotherapy. 2005 Jan;25(1):86-95. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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

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