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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00006066
First received: July 14, 2000
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine Adsorbed
Biological: Diphtheria and Tetanus Toxoids Adsorbed
Biological: Tetanus and Diphtheria Toxoids Adsorbed
Drug: Bacteriophage phi X 174
Drug: Aldesleukin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Subcutaneous IL-2 With Highly Active Antiretroviral Therapy in HIV-Infected Children With Immunosuppression

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 92
Study Completion Date: June 2006
Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006066

Locations
United States, California
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, California, United States, 90801
Usc La Nichd Crs
Los Angeles, California, United States, 90033
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States
UCSF Pediatric AIDS CRS
San Francisco, California, United States, 941430105
United States, District of Columbia
Children's National Med. Ctr., ACTU
Washington, District of Columbia, United States, 20060
Children's National Med. Ctr. Washington DC NICHD CRS
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Univ. of Miami Ped. Perinatal HIV/AIDS CRS
Miami, Florida, United States, 33161
USF - Tampa NICHD CRS
Tampa, Florida, United States, 33701
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 701122699
United States, Massachusetts
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States, 021155724
United States, New York
Nyu Ny Nichd Crs
New York, New York, United States, 10016
Columbia IMPAACT CRS
New York, New York, United States, 10032
SUNY Upstate Med. Univ., Dept. of Peds.
Syracuse, New York, United States, 13210
Puerto Rico
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Savita Pahwa
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00006066     History of Changes
Other Study ID Numbers: ACTG 402, 10607, PACTG 402
Study First Received: July 14, 2000
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Injections, Subcutaneous
Interleukin-2
Dose-Response Relationship, Drug
Drug Therapy, Combination
Immunocompromised Host
CD4 Lymphocyte Count
Anti-HIV Agents

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
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 31, 2014