Phase 3 N=1,695 Randomized Treatment

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

HIV Infection

Bottom Line

View on ClinicalTrials.gov: NCT00013611 ↗

Enrolled (actual)

1,695

Serious AEs

23.0%

Results posted

Dec 2010

Primary outcome: Primary: New or Recurrent Disease Progression Events, as Defined, or Death. — 110; 119 Participants — p=0.47

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Proleukin (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Minnesota
Primary completion: Jan 2007

Outcome Measures

Outcome	Result	p-value
PRIMARY New or Recurrent Disease Progression Events, as Defined, or Death.	110; 119	0.47
SECONDARY All-cause Mortality	81; 77	0.73
SECONDARY New or Recurrent Disease Progression Events	49; 66	0.10
SECONDARY Grade 4 Clinical Events	203; 186	0.35
SECONDARY CD4+ Cell Count	345.1; 292.1	< 0.001 sig
SECONDARY New or Recurrent Serious Disease Progression Events or Death	19; 28	—

Summary

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; ...

Eligibility Criteria

INCLUSION CRITERIA:

Subjects are eligible for this study if they have been on greater than or equal to 2 ART for greater than or equal to 4 months prior to randomization, with no change in the type of ART received during this 4-month period of time. For subjects who receive only 2 ART, at least one of these two medications should be a protease inhibitor (PI). Subjects are not eligible if ART is discontinued for a cumulative period of 7 or more days during the 4 months prior to randomization.

Subjects with documented HIV-1 infection. Acceptable documentation consists of either of the following:

Positive HIV-1 ELISA test and Western Blot;

Detectable plasma viral load measurement (greater than 500 RNA copies/mL using an ultrasensitive bDNA or PCR test or greater than 1500 RNA copies/mL using a non-ultrasensitive bDNA or PCR test).

CD4+ T cell counts: mean of 2 points obtained within 4 calendar months of randomization greater than or equal to 50 and less than 300 cells/mm(3). The first CD4+ count should be the most recent documented historical value and should be greater than or equal to 50 and less than 300 cells/mm(3); the second point should be pre-study visit 1.

Viral load less than 10,000 copies/mL, at 2 time points within 4 calendar months of randomization. The first viral load should be the most recent documented historical value and should be less than 10,000 copies/mL; the second time point should be pre-study visit 1.

Karnofsky performance status greater than or equal to 80%.

Age greater than or equal to 18 years old.

Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to randomization. They must also understand that if they are randomized to the IL-2 group, they must practice effective contraception during their first 2 years of study participation. Pregnancy is discouraged among IL-2 recipients, but if an IL-2 recipient wishes to become pregnant after two years of trial participation she must alert the investigator prior to interruption of contraception. The potential for risk to the fetus must be carefully discussed with the subject before contraception is interrupted. Effective contraception will be continued for at least 24 hours following the interruption of IL-2 therapy. IL-2 will be held throughout the period of time during which the subject is not practicing effective birth control, throughout the pregnancy, and throughout any period of breast feeding. If oral contraceptive therapy is resumed after a period of interruption, IL-2 dosing will be delayed for 1 month following the reinstatement of oral contraceptive therapy. The subject must have a negative pregnancy test result prior to dosing with IL-2 after a lapse in effective contraception.

The following laboratory criteria must be fulfilled within 28 days of enrollment in the study:

Serum AST of less than or equal to 5 times upper limit of normal range (ULN);

Serum bilirubin less than or equal 2 times ULN (patients with Gilbert's syndrome or protease inhibitor-induced hyperbilirubinemia must have a serum bilirubin less than or equal to five times ULN);

Amylase less than 2.0 times ULN (hyperamylasemia that is determined to be non-pancreatic in origin does not necessarily constitute an exclusion to enrollment);

Less than 2 + proteinuria;

Serum creatinine less than or equal to 1.5 times ULN;

Absolute neutrophil count greater than or equal to 1000 cells/mm(3);

Hemoglobin of greater than or equal to 9.5 g/dL;

Platelet count of greater than or equal to 75,000/mm(3);

Negative HTLV-1 result.

Agree to participate in the study for 4.5 to 7.5 years.

Written informed consent.

EXCLUSION CRITERIA

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 t

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Data sourced from ClinicalTrials.gov (NCT00013611). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.