A Phase II Study of Intermittent Recombinant Human Interleukin-2 (rhIL-2) by Intravenous or Subcutaneous Administration in Subjects With HIV Infection on Highly Active Antiretroviral Therapy (HAART) Compared to HAART Alone
7 other identifiers
interventional
200
1 country
20
Brief Summary
To compare two different routes of intermittently administered rhIL-2 with a highly active antiretroviral regimen (HAART) to HAART alone. The comparison is based on the following: proportion of patients achieving at least 50-percent increase in CD4 counts above prerandomization baseline values after 1 year of rhIL-2 and the rate of change in CD4 counts. To compare the safety and tolerance of these regimens and their effect on quality of life. To assess the effects of rhIL-2 when combined with HAART on changes in immune cell phenotypes and function and on HIV viral load and the rate of antiviral drug resistance development. The poor responsiveness of late stage HIV-infected patients to rhIL-2 is thought to occur because of low T cell regenerative capacity and high viral burden. If means were available to effectively suppress virus replication, the indigenous immune restorative responses of the host may be further stimulated and enhanced by rhIL-2. The use of protease inhibitors with nucleoside-analogue combination regimens appears to be most effective in controlling virus replication. High-dose intermittent rhIL-2 administered either intravenously or subcutaneously has been shown to be effective in inducing CD4 responses in a number of studies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 hiv-infections
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2007
CompletedMay 21, 2012
May 1, 2012
November 2, 1999
May 17, 2012
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- Required:
- Patients must be able to initiate one of the following nucleoside analogue regimens of which at least one of the drugs must be new to the patient:
- ZDV + 3TC, ZDV + ddI, d4T + 3TC, or d4T + ddI. \[AS PER AMENDMENT 4/5/00: ddI is contraindicated in patients with serum amylase or lipase values greater than 1.5 x ULN or who have a history of pancreatitis. ddI should also be used with extreme caution and only if clinically indicated in patients with known risk factors. For more information, see package insert.\]
- Allowed:
- Prophylaxis for Pneumocystis carinii pneumonia and other opportunistic infections according to current CDC recommendations. Prophylaxis, once started, should be continued despite increases in CD4 counts during the course of the study.
- Any standard regimen for an opportunistic infection.
- Maintenance therapy for opportunistic infections that develop on study treatment is permitted according to standard medical care; except for foscarnet during rhIL-2 administration and rifabutin and rifampin.
- Maintenance therapy with \<= 1000 mg/day of acyclovir is permitted for recurrent genital herpes.
- Erythropoietin and filgrastim (G-CSF) are permitted when clinically indicated.
- Antibiotics for bacterial infections are permitted as clinically indicated.
- Medications for symptomatic treatment such as antipyretics and analgesics are permitted. Ibuprofen and acetaminophen are the preferred agents.
- Any elective standard immunizations, e.g., flu shot, should be given no less than 4 weeks prior to any blood draw for HIV RNA by bDNA assay.
- Topical corticosteroid use provided applied to a site separate from any skin test or rhIL-2 injection site (if frequent therapy is required for large surface area, protocol chair must be contacted).
- Concurrent Treatment:
- +10 more criteria
You may not qualify if:
- Co-existing Condition:
- Patients with the following symptoms and conditions are excluded:
- Any active AIDS-defining illness by the CDC case definition with the exception of minimal (less than 10 lesions) cutaneous Kaposi's sarcoma.
- Significant cardiac insufficiency (NYHA grade 2). Patients with isolated hypertension controlled by antihypertensive medication but no cardiac disease are eligible.
- Untreated thyroid disease (treated and stable hyperthyroidism or hypothyroidism for at least 4 weeks prior to study entry is permitted).
- Sensitivity to albumin or allergy to albumin.
- Concurrent Medication:
- Excluded:
- Concurrent treatment with investigational antiretroviral agents other than FDA-sanctioned treatment IND drugs.
- Treatment for active cardiac disease, with the following medications: anti-anginal agents such as nitrates, calcium channel blockers, beta blockers, antiarrhythmics including digitalis and afterload reducers.
- Patients with malignancy requiring treatment with systemic or local cytotoxic chemotherapy.
- Prohibited medications:
- interferons, interleukins (other than the study rhIL-2), sargramostim, dinitrochlorobenzene, thymosin alpha 1, thymopentin, inosiplex, polyribonucleoside, ditiocarb sodium, thalidomide, rifabutin, rifampin, midazolam, triazolam, oral ketoconazole, cisapride, terfenadine, astemizole, any investigational drug, therapy with foscarnet, systemic corticosteroids (systemic corticosteroids for \<= 21 days are permitted for treatment of Pneumocystis carinii pneumonia; for other indications, contact the Protocol Chair), and other protease inhibitors. \[AS PER AMENDMENT 4/5/00: St. John's wort is also excluded.\]
- Patients with the following prior conditions are excluded:
- History of autoimmune disease, including inflammatory bowel disease and psoriasis (stable autoimmune thyroid disease is permitted).
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Alabama Therapeutics CRS
Birmingham, Alabama, 35294, United States
USC CRS
Los Angeles, California, 900331079, United States
Stanford CRS
Palo Alto, California, 943055107, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502, United States
University of Colorado Hospital CRS
Aurora, Colorado, 80262, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, 52242, United States
Tulane Univ. A1701 CRS
New Orleans, Louisiana, 70112, United States
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, 02215, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63112, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003, United States
NY Univ. HIV/AIDS CRS
New York, New York, 10016, United States
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, 10021, United States
Mt. Sinai Med. Ctr. (N.Y.) A1801 CRS
New York, New York, 10029, United States
Unc Aids Crs
Chapel Hill, North Carolina, 275997215, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710, United States
Case CRS
Cleveland, Ohio, 44106, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 432101228, United States
Univ. of Texas Medical Branch, ACTU
Galveston, Texas, 775550435, United States
University of Washington AIDS CRS
Seattle, Washington, 981224304, United States
Related Publications (4)
Reier A, Mitsuyasu RT. Use of interleukin-2 in immunotherapy of human immunodeficiency virus infection. BioDrugs. 1998 Sep;10(3):215-25. doi: 10.2165/00063030-199810030-00005.
PMID: 18020597BACKGROUNDBucy RP, Hockett RD, Derdeyn CA, Saag MS, Squires K, Sillers M, Mitsuyasu RT, Kilby JM. Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest. 1999 May 15;103(10):1391-8. doi: 10.1172/JCI5863.
PMID: 10330421BACKGROUNDMitsuyasu R, Pollard R, Gelman R, Weng D. Prospective, randomized, controlled phase II study of highly active antiretroviral therapy (HAART) with continuous IV (CIV) or subcutaneous (SC) interleukin-2 (IL-2) in HIV-infected patients with CD4+counts of 50-350 cells/mm3: ACTG 328-final results at 84 weeks. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 17)
BACKGROUNDHockett RD, Kilby JM, Derdeyn CA, Saag MS, Sillers M, Squires K, Chiz S, Nowak MA, Shaw GM, Bucy RP. Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA. J Exp Med. 1999 May 17;189(10):1545-54. doi: 10.1084/jem.189.10.1545.
PMID: 10330433BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Ronald Mitsuyasu
- STUDY CHAIR
Richard Pollard
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Purpose
- TREATMENT
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 1999
First Posted
August 31, 2001
Study Completion
March 1, 2007
Last Updated
May 21, 2012
Record last verified: 2012-05