Clinical trial NCT00000849: A Study to Test the Safety of Recombinant Interleukin-2 (rIL-2) in HIV-Infected Children
Official title: Phase I/II Trial of Recombinant Interleukin-2 In Symptomatic Human Immunodeficiency Virus-Infected Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Interleukin-2
Immunity, Cellular
Dose-Response Relationship, Drug
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 27
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and maximum tolerated dose (the highest dose that can be given safely) of recombinant Interleukin-2 (rIL-2) in HIV-infected children. This study also evaluates the effect of rIL-2 on the immune system of these patients.

IL-2 is a substance naturally produced by the body's white blood cells that plays an important role in helping the body fight infection. HIV-infected patients do not produce enough IL-2, and it is hoped that the use of rIL-2 may improve immune system function in these patients. First, it is necessary to determine the safety and effectiveness of this drug in HIV-infected children.

Detailed description: According to study records, IL-2 has not been tested in HIV-infected children. Experience with IL-2 in pediatric populations is extremely limited. Pahwa et al. gave 30,000 units/kg daily IV to a child with severe combined immunodeficiency. This dose was well tolerated and the patient improved clinically as well as immunologically. Part A is necessary to determine the maximum tolerated dose of IL-2 in infected children. Part B will determine the efficacy of the maximum tolerated dose in infected children.

Part A: Children will receive rIL-2 intravenously for 5 days every 8 weeks for 3 cycles. The study will enroll 4 patients in each of 3 dose levels. Dose escalation may occur if all 4 patients in a dose level tolerate therapy without evidence of Grade 3 (or higher) toxicity. If 1 of 4 subjects in any dose level experiences at least Grade 3 toxicity, 2 additional patients will be enrolled in that dose level. If 1 of these 2 additional patients experiences at least Grade 3 toxicity, dose escalation will not proceed. NOTE: Once Part A is completed and the maximum tolerated dose is established, children who participated in Part A and received less than the maximum tolerated dose will be offered additional therapy consisting of 3 cycles of rIL-2 at the maximum tolerated dose.

Part B: Children will receive rIL-2 intravenously at the maximum tolerated dose established in part A. Treatment will be given for 5 days every 8 weeks for 3 cycles. \[AS PER AMENDMENT 6/4/98: Children will receive rIL-2 intravenously at the lowest dose for 5 days every 8 weeks for 6 cycles. Patients who received this dose in part A will also be offered this regimen.\]

Eligibility criteria: Inclusion Criteria

Children may be eligible for this study if they:

* Are HIV-positive.
* Have decreased immune system functioning (CD4 count 500-1000 for 3- to 5-year-olds or CD4 count 200-500 for 6- to 12-year-olds).
* Have symptomatic HIV infection.
* Have a viral level less than 400 copies/ml.
* Are between the ages of 3 and 12 (consent of parent or guardian required).

Exclusion Criteria

Children will not be eligible for this study if they:

* Have an active opportunistic infection.
* Are pregnant.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Richmond
country: United States
facility: VCU Health Systems, Dept. of Peds
state: Virginia
Study officials:
name: Stuart Starr
role: STUDY_CHAIR
name: Steven Douglas
role: STUDY_CHAIR
References:
citation: Zeng C, Mawhinney S, Baron AE, McFarland EJ. Evaluating ELISPOT summary measures with criteria for obtaining reliable estimates. J Immunol Methods. 2005 Feb;297(1-2):97-108. doi: 10.1016/j.jim.2004.12.006.