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

NCT ID: NCT00110812

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2011-02-28

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.

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

Keywords

Treatment Naive; IL-2; rIL-2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No IL-2

Participants will receive no aldesleukin or HAART

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

IL-2

Intervention Type: DRUG

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)

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.

Group Type: EXPERIMENTAL

IL-2

Intervention Type: DRUG

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)

Interventions

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 Type: DRUG

Other Intervention Names

Proleukin, Aldeskeukin

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiron Corporation

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jorge Tavel, MD

Role: STUDY_CHAIR

National Institute for Allergy and Infectious Diseases, National Institutes of Health

Locations

VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS

Los Angeles, California, United States

Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS

Washington D.C., District of Columbia, United States

NIH Clinical Ctr., NIAID HIV Clinic CRS

Bethesda, Maryland, United States

Henry Ford Hosp. CRS

Detroit, Michigan, United States

Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)

New York, New York, United States

Lincoln Hosp. & Med. Ctr. CRS

The Bronx, New York, United States

Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS

Portland, Oregon, United States

Michael E. DeBakey VAMC CRS

Houston, Texas, United States

Thomas Street Clinic CRS

Houston, Texas, United States

South Texas Veterans Health Care System, Immunosuppression Clinic CRS

San Antonio, Texas, United States

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, United States

Hosp. Italiano de Buenos Aires, Infectious Diseases Section 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

Funcei Crs

Ciudad de Buenos Aires, Buenos Aires, Argentina

Caici Crs

Rosario, Provincia de Sante Fe, Argentina

St. Vincent's Hospital CRS

Darlinghurst, New South Wales, Australia

Queensland Health - AIDS Med. Unit CRS

Brisbane, Queensland, Australia

Gladstone Road Medical Ctr. CRS

Highgate Hill, Queensland, Australia

Gold Coast Sexual Health Clinic CRS

Miami, Queensland, Australia

Carlton Clinic CRS

Carlton, Victoria, Australia

Fundacion Arriaran CRS

Santiago, , Chile

Ospedale San Raffaele S.r.l. CRS

Milan, , Italy

Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS

Milan, , Italy

Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS

Casablanca, , Morocco

Wojewodzki Szpital Zakazny CRS

Warsaw, , Poland

Hospital de Cascais, HDDI, Departamento Medicina Interna CRS

Cascais, , Portugal

Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS

Lisbon, , Portugal

Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS

Lisbon, , Portugal

Hosp. Clinico de Barcelona CRS

Barcelona, , Spain

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

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 Kingdom

Countries

Germany; Ireland; Seychelles; The Gambia; United States; Argentina; Australia; Chile; Italy; Morocco; Poland; Portugal; Spain; Thailand; United Kingdom

References

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Reference Type: BACKGROUND

PMID: 15767224 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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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. doi: 10.1093/jac/dkh557. Epub 2005 Feb 24.

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Pett 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.

Reference Type: BACKGROUND

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Tavel 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.

Reference Type: DERIVED

PMID: 20186278 (View on PubMed)

Other Identifiers

10053

Identifier Type: REGISTRY

Identifier Source: secondary_id

ESPRIT 002

Identifier Type: -

Identifier Source: org_study_id

NCT00106730

Identifier Type: -

Identifier Source: nct_alias