Interleukin-2 Plus Anti-HIV Therapy in HIV-Infected Children With Weakened Immune Systems

HIV Infections Clinical Trial

Official title:

Phase I/II Trial of Subcutaneous IL-2 With Highly Active Antiretroviral Therapy in HIV-Infected Children With Immunosuppression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006066
• Other study ID #: ACTG 402
• Secondary ID: 10607PACTG 402
• Status: Completed
• Phase: Phase 1
• Est. completion date: June 2006

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety of a drug called interleukin-2 (IL-2) given with anti-HIV therapy in children with HIV infection. This study will also determine the best dose of IL-2 to give children.

IL-2 is an important substance produced by the body's white blood cells that helps the body fight infection. People with HIV infection do not produce enough IL-2. It is hoped that IL-2 treatment will help boost the immune system in people with HIV infection. It has not been studied very much in children and doctors need to know what doses are safe to give.

Description:

One of the challenges in effective combination therapy in HIV-infected patients is the ability to achieve immune reconstitution. IL-2 is hypothesized to restore and/or preserve the immune system when added to potent antiretroviral regimens. This study will evaluate restoration of immune functions of CD4 cells and will also determine the best way to deliver IL-2 in a safe and effective way.

Part I: Patients add a 5-day course of subcutaneous IL-2 every 8 weeks for up to 48 weeks (6 cycles) to their HAART therapy. Three dose levels of IL-2 are administered. [AS PER AMENDMENT 5/3/01: It is strongly recommended, but not required, that] the first and second cycles of IL-2 are given in the hospital on an inpatient basis. The parent or patient is trained to give the injections and has the option of administering subsequent injections at home. Patients are monitored for CD4 and CD8 cell count and viral load. Enrollment into Part 1 begins at the lowest dose level; assuming no serious toxicities (Grade 3 or higher) occur, patients are enrolled into higher dose levels. The highest tolerated dose is established.

Part 2: After the highest tolerated dose is established in Part 1, additional patients are randomized to receive HAART alone (Arm 1), HAART with high-dose IL-2 (Arm 2), or HAART with low-dose IL-2 (Arm 3). High-dose IL-2 is given twice daily at the highest dose tolerated in Part 1 for 5 days every 8 weeks for 6 cycles. Low-dose IL-2 is given once a day every day for 48 weeks. For Arms 2 and 3 [AS PER AMENDMENT 5/3/01: (except patients in the pharmacokinetic substudy), it is strongly recommended, but not required, that] IL-2 is given the first week on an inpatient basis by hospital personnel. As in Part 1, there is the option of administering the remaining injections at home. Intensive toxicity monitoring, routine lymphocyte subsets, and quantitative HIV RNA are performed on all patients at specified time points during the study. The first 12 patients in Arms 2 and 3 have pharmacokinetic testing with frequent blood samples drawn at intervals, some of which require staying up to 12 hours at the clinic. Diphtheria/tetanus immunizations and bacteriophage phi X174 immunizations are administered to all patients to determine antibody responses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria

A child may be eligible for this trial if he/she:

• Is HIV-positive.

• Is 2 to 18 years old (consent of parent or guardian required if under 18).

• Has received 12 or more weeks of anti-HIV drug therapy, consisting of at least 3 drugs. This combination may include a nucleoside reverse transcriptase inhibitor (NRTI), a nonnucleoside reverse transcriptase inhibitor, or a protease inhibitor, or 3 NRTIs. Combinations of NRTIs may not include abacavir (ABC). Patients may have taken ABC if it was not in combination with 2 other NRTIs. (This reflects a change in the requirement for anti-HIV therapy.)

• Has a plasma HIV RNA level of less than 10,000 copies/ml.

• Has evidence of a weakened immune system (based on CD4 cell counts and absolute CD4 percentage less than 25 percent). (This reflects a change in how a weakened immune system is defined.)

• Has a parent or guardian who is willing to comply with study requirements.

• Has symptoms of HIV infection.

Exclusion Criteria

A child will not be eligible for this study if he/she:

• Has an active opportunistic (AIDS-related) infection.

• Is pregnant.

• Is taking certain medications, such as steroids or other drugs that affect the immune system, within 6 weeks prior to study entry.

• Is taking ABC.

• Is taking certain antibodies.

• (Exclusion criteria reflect changes.)

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine Adsorbed

• Diphtheria and Tetanus Toxoids Adsorbed

• Tetanus and Diphtheria Toxoids Adsorbed

Drug:
• Bacteriophage phi X 174

• Aldesleukin

Locations

Country	Name	City	State
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Nyu Ny Nichd Crs	New York	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	USF - Tampa NICHD CRS	Tampa	Florida
United States	Children's National Med. Ctr. Washington DC NICHD CRS	Washington	District of Columbia
United States	Children's National Med. Ctr., ACTU	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

External Links

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