Interleukin-2 Plus Antiretroviral Therapy for HIV-Infected Patients With Low CD4+ Counts (SILCAAT Study)

Completed · Phase 3

Conditions studied: HIV Infection

In brief

This study will examine whether interleukin-2 (IL-2) plus antiretroviral therapy (ART) slows HIV disease progression in patients with low CD4+ T cell counts compared with patients taking ART alone. CD4+ T cells are a subset of lymphocytes-white blood cells that are part of the body's immune system. IL-2 is a protein that is naturally produced by lymphocytes. Given in intermittent cycles, IL-2 can raise CD4+ T cell counts in some HIV-infected patients taking antiretroviral drugs. This study will examine whether the increase in CD4+ T cells lowers the risk of AIDS-related illnesses and death. HIV-infected patients 18 years of age and older with a viral load under 10,000 copies per milliliter and a CD4+ T cell count between 50 and 299 cells per cubic millimeter who are taking antiretroviral therapy and who have not previously received IL-2 therapy may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Participation in the study will be from 4.5 to 6 years, depending on what point in the duration of the study the individual patient is enrolled. Patients will be randomly assigned to receive IL-2 plus ART or ART alone. All participants will be advised individually about the best ART regimen for them. Patients in the IL-2 treatment group will be taught how to self-inject IL-2 under the skin (similar to insulin injections). They will inject IL-2 twice a day for 5 days every 8 weeks for the first year (until week 49 of the study). From week 49 on they may receive 5-day cycles of IL-2 every 4 months when needed to maintain CD4+ T cell count elevations. An extra cycle may be given 2 months after the week 49 follow-up visit (see follow-up schedule below), depending on their CD4+ T cell count. Patients whose cell counts have not increased after 12 to 16 months of IL-2 treatment will discuss with the doctor the possibility of stopping IL-2. Those who do stop IL-2 treatment will be asked to remain in the study for follow-up evaluations. All patients will be followed in the clinic every 2 months for the first year of the study (weeks 1, 9, 17, 25, 33, 41 and 49) and every 4 months during years 2-6 for a brief history and physical exam, urine and blood tests, return of diary cards (record of drug side effects) and medication review. During the visits from the second year on, patients will also be asked about their ability to do certain ordinary tasks, such as taking care of themselves; ...

Key facts

Study ID

NCT00013611

Run by

University of Minnesota

People needed

1695

Starts

2001-03-01

Expected to finish

2007-01-01

Last updated by the study team

2011-08-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Certain AIDS-defining illnesses. These conditions include:
• Patients with no prior history of AIDS-defining events are eligible for SILCAAT;
• Patients with a prior medical history of one or more of the following AIDS-defining events are eligible only under the condition specified below:
• Lymphoma (other than lymphoma of the brain): Patients with a history of successfully treated lymphoma are eligible, provided full remission was obtained at least 5 years prior to randomization. Full remission (or complete response) is defined as the absence of clinically detectable disease with normalization of any previously abnormal radiographic studies, and bone marrow examination. Patients with bone marrow positive lymphoma prior to chemotherapy must have had two repeat bone marrow examinations negative for lymphoma after chemotherapy at least 12 months prior to randomization.
• Esophageal candidiasis; Patients with a prior history of successfully treated esophageal candidiasis are eligible if they have been free of clinical symptoms in the absence of antifungal suppressive therapy for at least 12 months prior to randomization. Documentation of a negative endoscopy should ideally be on record.
• Invasive cervical cancer: Patients with a prior history of invasive cervical cancer are eligible if complete local cure of the cancer has been documented at least 5 years prior to randomization and there has been no evidence of metastatic disease at any time.
• Kaposi's sarcoma: Patients are eligible if mucocutaneous lesions have been resolved or clinically stable for at least 12 months prior to randomization. Subjects with a history of visceral KS are excluded.
• Mycobacterium tuberculosis or M. kansasii: Patients are eligible if clinical resolution of disease occurred at least 12 months prior to randomization and previously abnormal imaging studies have been normal, or stable after improvement, for at least 12 months prior to randomization. Documentation of microbiologic cure should ideally be on record. Therapy for tuberculosis or M. kansasii must have been completed at least 12 months prior to randomization.
• Pneumocystis carinii pneumonia (PCP): Patients are eligible if clinical resolution of the disease occurred at least 12 months prior to randomization and previously abnormal imaging studies have been normal, or stable after improvement, for at least 12 months prior to randomization.
• Recurrent pneumonia: Patients are eligible if there has been no evidence of pneumonia within 12 months prior to randomization.
• Recurrent Salmonella septicemia: Patients are eligible if there has been no evidence of Salmonella septicemia within 12 months prior to randomization.
• Wasting syndrome due to HIV: Patients are eligible for enrollment in SILCAAT if they have had a stable or increasing weight for at least 12 months prior to randomization.
• Toxoplasmosis of the brain: Patients are eligible if their disease has been clinically resolved for at least 12 months prior to randomization. In addition, these patients must have a MRI or contrast CT scan of the brain performed within 1 month prior to randomization showing no sign of active disease.
• Chronic intestinal cryptosporidiosis and chronic intestinal isosporiasis (greater than 1 month duration): Patients are eligible if their disease has been clinically resolved and they have been off specific therapy for at least 12 months prior to randomization. In addition, these patients must have at least one stool specimen documenting clearance of parasitic infection obtained within 1 month prior to randomization.
• Patients with a history of any other AIDS-defining conditions as listed in the CDC 1993 Case Definition are not eligible for SILCAAT.
• Subjects must not have clinically significant cardiac, pulmonary, thyroid, kidney or neurologic impairment, hemostasis disorder, or significant medical condition that would, in the opinion of the principal investigator, affect patient safety and/or compliance. In addition, subjects with the following conditions are specifically excluded: autoimmune disease, inflammatory bowel disease, psoriasis, optic neuritis, congestive heart failure, active ischemic heart disease, uncontrolled diabetes mellitus, moderate or severe hemophilia ( less than or equal to 5% of normal factor VIII levels), seizure disorder, uncontrolled hypothyroidism, cirrhosis and a prior medical history of transplantation. If an investigator has any reservations about the safety of enrolling a particular subject, he/she should consult with the medical monitor prior to screening the subject.
• Psychiatric or cognitive disturbance or illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance.
• Malignancy requiring systemic chemotherapy within 12 months prior to randomization.
• Current use or use within 4 weeks prior to randomization of systemic corticosteroid therapy or any agent, licensed or experimental, with known immunomodulatory effects (use of erythropoietin and anabolic steroids is allowed).
• Current use, or use within 4 weeks of randomization of cytotoxic agents or antimetabolites; current use or use within 4 months of randomization of hydroxyurea or intravenous immunoglobulin.
• Pregnant or lactating subjects.
• Prior therapy with IL-2.
• Prior participation in an ongoing IL-2 trial, eg, the ESPRIT trial.
• Protocol non-compliance in a previous IL-2 trial.
• Subjects with evidence of active acute infection within 2 weeks of randomization.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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