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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00110812
First received: May 13, 2005
Last updated: May 24, 2012
Last verified: May 2012
  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: Aldesleukin
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: A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 (rIL-2, Aldesleukin) With and Without Concomitant Antiretroviral Therapy in Patients With HIV-1 Infection and CD4+ Cell Counts of 300 Cells/mm3 or More: Study of Aldesleukin With and Without Concomitant Antiretroviral Therapy

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: Through Week 32 ] [ Designated as safety issue: No ]
  • HIV disease progression events and death between IL-2 recipients and controls [ Time Frame: At Month 31 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Grade 3 and 4 events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Therapy modification as defined by the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Plasma HIV RNA [ Time Frame: At Week 32, Month 12, and Month 31 ] [ Designated as safety issue: No ]
  • CD4 T lymphocyte count [ Time Frame: At Months 12 and 31 ] [ Designated as safety issue: No ]
  • HIV-1 genotype changes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Fasting lipid profile and thyroid stimulating hormone and hepatic transaminase levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Timing of commencement of continuous antiretrovirals [ Time Frame: At Month 31 ] [ Designated as safety issue: No ]

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: 1
Participants will receive no aldesleukin or HAART
Experimental: 2
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: Aldesleukin
7.5 MIU injected intramuscularly
Other Name: Proleukin
Experimental: 3
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.
Drug: Aldesleukin
7.5 MIU injected intramuscularly
Other Name: Proleukin

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00110812

  Show 36 Study Locations
Sponsors and Collaborators
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
Last Updated: May 24, 2012
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:
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
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 15, 2014