Pharmacodynamics of Intermittent IL-2 Infusions in HIV Seropositive Patients

Phase 2

Completed

• Conditions: HIV Infection

• Registration Number: NCT00001474
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

This study is designed as a randomized, open trial of intermittent continuous infusions of Interleukin-2 in HIV seropositive patients with a CD4 cell count between 200 and 500 cells/mm(3). The goal of the study is to determine the optimal duration of each infusion, and the optimal interval between infusions. Thirty-six patients will be randomized to 3 groups: Group A will be the control group with a regimen of five day infusions of IL-2 every eight weeks; Group B will receive IL-2 infusions every eight weeks, however the duration of each infusion will be determined by parameters reflecting T cell proliferation, with discontinuation of each infusion at a point when the response appears to be maximized; Group C will receive five day infusions of IL-2; however the interval between infusions will be determined by the response seen to the prior infusion, with the goal of administering infusions while the CD4 cell count remains above baseline from the prior infusion. The dose of interleukin-2 to be used will be 9 MIU by continuous infusion daily. All patients will be evaluated at the NIH at least every 4 weeks, and at that time safety labs and immune studies will be performed. In addition, patients in Groups B and C will undergo a laboratory evaluation weekly, at which time immune parameters, including CD4 number and percent, spontaneous blast transformation, soluble IL-2 receptor levels, and viral parameters, including branched DNA assay and p24 antigen, will be determined. The study duration will be approximately one year.

Detailed Description

This study is designed as a randomized, open trial of intermittent continuous infusions of Interleukin-2 in HIV seropositive patients with a CD4 cell count between 200 and 500 cells/mm(3). The goal of the study is to determine the optimal duration of each infusion, and the optimal interval between infusions. Thirty-six patients will be randomized to 3 groups: Group A will be the control group with a regimen of five day infusions of IL-2 every eight weeks; Group B will receive IL-2 infusions every eight weeks, however the duration of each infusion will be determined by parameters reflecting T cell proliferation, with discontinuation of each infusion at a point when the response appears to be maximized; Group C will receive five day infusions of IL-2; however the interval between infusions will be determined by the response seen to the prior infusion, with the goal of administering infusions while the CD4 cell count remains above baseline from the prior infusion. The dose of interleukin-2 to be used will be 9 MIU by continuous infusion daily. All patients will be evaluated at the NIH at least every 4 weeks, and at that time safety labs and immune studies will be performed. In addition, patients in Groups B and C will undergo a laboratory evaluation weekly, at which time immune parameters, including CD4 number and percent, spontaneous blast transformation, soluble IL-2 receptor levels, and viral parameters, including branched DNA assay and p24 antigen, will be determined. The study duration will be approximately one year.

Significant modifications to the original protocol described above, have included:

1. altering the number of cycles Group B and Group C participants receive at increased frequency or duration;

2. dropping Group B from the original randomization process;

3. providing continuing administration of IL-2 after the first year of the protocol;

4. changing the target CD4+ count below which participants in extension will receive additional cycle(s) of IL-2;

5. increasing the blood volume to be drawn at each visit to accommodate additional storage of plasma and serum;

6. administering corticosteroids for up to 5 days during IL-2 administration to patients who fail to respond to IL-2 after at least one year of administration;

7. providing for participants to receive intravenous IL-2 on an outpatient basis without the assistance of a caregiver;

8. administering individualized IL-2 regimens for all patients after the first year of participation. It also provided for a revised patient monitoring schedule in keeping with other IL-2 protocols and for long-term monitoring of patients no longer receiving IL-2.

9. modification of steroid administration to allow 7-day therapy and tapering schedule;

10. allowing the use of non-licensed, but expanded access anti-retrovirals;

11. allowing, in select subjects, at home (off-site) self-administration of IL-2.

Study Timeline

• Study Start: 1995-05
• Study First Submitted: 1999-11-03
• Study First Submitted QC: 1999-11-03
• Study First Posted: 1999-11-04
• Status Verified: 2002-03
• Study Completion: 2002-03
• Last Update Submitted: 2008-03-03
• Last Update Posted: 2008-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

National Institute of Allergy and Infectious Diseases (NIAID); 🇺🇸 Bethesda, Maryland, United States