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The Safety and Effectiveness of Interleukin-2 Plus Zidovudine in Patients With AIDS or AIDS Related Complex

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Aldesleukin
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Recombinant Proteins, Interleukin-2, Drug Interactions, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Acetaminophen under the supervision of a study physician. Prior Medication: Required for at least 6 weeks prior to study entry: Zidovudine at a dose of at least 300 mg/day. Allowed: Aerosolized pentamidine prior to combination therapy. Patients must demonstrate the following clinical and laboratory findings: Currently receiving zidovudine (AZT) at a dose of at least 300 mg/day and have received the drug for at least 6 weeks. Have a life expectancy of = or > 4 months. Available for the duration of the study and for follow-up visits. Exclusion Criteria Co-existing Condition: Patients with the following conditions will be excluded: Evidence of active life-threatening opportunistic infection with bacterial, viral, fungal, or protozoan pathogens during the 6-week period prior to and during the 5-day period of combination therapy. A fever > 101 degrees F within the past 10 days. Significant central nervous system disease, including acquired immunodeficiency syndrome (AIDS), dementia, psychiatric disabilities, or seizure disorders. Significant cardiac (New York Heart Association stage III or IV) and/or pulmonary disease (forced expiratory volume < 75 percent). Kaposi's sarcoma or other AIDS related malignancy. Evidence of malabsorption as indicated by 10 percent weight loss within the last 3 months. Concurrent Medication: Excluded: Cardiac medications. Glucocorticosteroids. Probenecid. Acetylsalicylic acid. Trimethoprim / sulfamethoxazole. Acyclovir. Allopurinol. Drugs causing anemia, neutropenia, or nephrotoxicity. Aerosolized pentamidine during combination therapy. Nonsteroidal anti-inflammatory drugs by patients with thrombocytopenia (<75000 platelets/mm3). Acetaminophen except under supervision of a study physician. Patients with the following conditions will be excluded: Evidence of active life-threatening opportunistic infection with bacterial, viral, fungal, or protozoan pathogens during the 6-week period prior to and during the 5-day period of combination therapy. A fever > 101 degrees F within the past 10 days. Significant central nervous system disease, including acquired immunodeficiency syndrome (AIDS), dementia, psychiatric disabilities, or seizure disorders. Significant cardiac (New York Heart Association stage III or IV) and/or pulmonary disease (forced expiratory volume < 75 percent). Kaposi's sarcoma or other AIDS related malignancy. Evidence of malabsorption as indicated by 10 percent weight loss within the last 3 months. Prior Medication: Excluded within 4 weeks of study entry: Any antiretroviral drug, except zidovudine (AZT). Excluded within 12 weeks of study entry: Immunotherapy, including interleukins, interferons, tumor necrosis factor. Other cytokines. Biologic response modifiers. Monoclonal antibodies. BCG vaccines. Active drug or alcohol abuse.

Sites / Locations

  • Univ of Pittsburgh Med School

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000986
Brief Title
The Safety and Effectiveness of Interleukin-2 Plus Zidovudine in Patients With AIDS or AIDS Related Complex
Official Title
A Safety, Tolerance, and Immunological Study of a Combination of Recombinant Interleukin 2 and Zidovudine in Patients With AIDS or AIDS Related Complex
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 1994 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
To test the safety and tolerance of three different doses of recombinant human interleukin 2 (aldesleukin; IL-2), when it is given for five consecutive days to patients with AIDS or AIDS related complex (ARC), who have also received zidovudine (AZT) for at least 6 weeks just before beginning the IL-2 treatment. AZT is an antiviral drug, which has been shown to be beneficial in some patients with AIDS. IL-2 is a substance found naturally in the body that boosts the body's immune response to invading organisms and tumor cells. These two drugs, when administered together, may have a mutually helpful effect in treating AIDS patients, but before this effect can be studied, it is important to understand the proper dose and any side effects that may occur when these drugs are used together. The study will show how much AZT and IL-2 patients can safely take at the same time and how the two drugs will interact with each other.
Detailed Description
AZT is an antiviral drug, which has been shown to be beneficial in some patients with AIDS. IL-2 is a substance found naturally in the body that boosts the body's immune response to invading organisms and tumor cells. These two drugs, when administered together, may have a mutually helpful effect in treating AIDS patients, but before this effect can be studied, it is important to understand the proper dose and any side effects that may occur when these drugs are used together. The study will show how much AZT and IL-2 patients can safely take at the same time and how the two drugs will interact with each other. AMENDED: Note that the dose of AZT changed 900214 to reflect new dose recommendations. Original design: Six weeks before beginning treatment with IL-2, patients are given AZT daily. There are three patient groups, one for each dose level of IL-2. On the first day of treatment with the two drugs together, patients are admitted to Presbyterian University Hospital, where AZT is administered orally every 4 hours and IL-2 is given once a day as a single injection under the skin. Clinical and laboratory safety data from the first two patients enrolled in each treatment group will be analyzed prior to enrolling additional patients in each group. All patients are expected to stay in the hospital for at least 5 days, and some may stay longer if serious side effects develop. AZT treatment will continue after the patient leaves the hospital for an additional 10 weeks. Follow-up visits are scheduled for days 6, 8, and 15 for safety, immunologic, and virologic evaluations. Thereafter, patients are followed by telephone interview every other week and come into the clinic if a change in health is reported. At weeks 10 and 20, patients are also evaluated in a follow-up clinic visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Recombinant Proteins, Interleukin-2, Drug Interactions, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
18 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Aldesleukin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Acetaminophen under the supervision of a study physician. Prior Medication: Required for at least 6 weeks prior to study entry: Zidovudine at a dose of at least 300 mg/day. Allowed: Aerosolized pentamidine prior to combination therapy. Patients must demonstrate the following clinical and laboratory findings: Currently receiving zidovudine (AZT) at a dose of at least 300 mg/day and have received the drug for at least 6 weeks. Have a life expectancy of = or > 4 months. Available for the duration of the study and for follow-up visits. Exclusion Criteria Co-existing Condition: Patients with the following conditions will be excluded: Evidence of active life-threatening opportunistic infection with bacterial, viral, fungal, or protozoan pathogens during the 6-week period prior to and during the 5-day period of combination therapy. A fever > 101 degrees F within the past 10 days. Significant central nervous system disease, including acquired immunodeficiency syndrome (AIDS), dementia, psychiatric disabilities, or seizure disorders. Significant cardiac (New York Heart Association stage III or IV) and/or pulmonary disease (forced expiratory volume < 75 percent). Kaposi's sarcoma or other AIDS related malignancy. Evidence of malabsorption as indicated by 10 percent weight loss within the last 3 months. Concurrent Medication: Excluded: Cardiac medications. Glucocorticosteroids. Probenecid. Acetylsalicylic acid. Trimethoprim / sulfamethoxazole. Acyclovir. Allopurinol. Drugs causing anemia, neutropenia, or nephrotoxicity. Aerosolized pentamidine during combination therapy. Nonsteroidal anti-inflammatory drugs by patients with thrombocytopenia (<75000 platelets/mm3). Acetaminophen except under supervision of a study physician. Patients with the following conditions will be excluded: Evidence of active life-threatening opportunistic infection with bacterial, viral, fungal, or protozoan pathogens during the 6-week period prior to and during the 5-day period of combination therapy. A fever > 101 degrees F within the past 10 days. Significant central nervous system disease, including acquired immunodeficiency syndrome (AIDS), dementia, psychiatric disabilities, or seizure disorders. Significant cardiac (New York Heart Association stage III or IV) and/or pulmonary disease (forced expiratory volume < 75 percent). Kaposi's sarcoma or other AIDS related malignancy. Evidence of malabsorption as indicated by 10 percent weight loss within the last 3 months. Prior Medication: Excluded within 4 weeks of study entry: Any antiretroviral drug, except zidovudine (AZT). Excluded within 12 weeks of study entry: Immunotherapy, including interleukins, interferons, tumor necrosis factor. Other cytokines. Biologic response modifiers. Monoclonal antibodies. BCG vaccines. Active drug or alcohol abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M Ho
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Pittsburgh Med School
City
Pittsburgh
State/Province
Pennsylvania
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8011237
Citation
McMahon DK, Armstrong JA, Huang XL, Rinaldo CR Jr, Gupta P, Whiteside TL, Pazin GJ, Tripoli C, Ho M. A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine. AIDS. 1994 Jan;8(1):59-66. doi: 10.1097/00002030-199401000-00009.
Results Reference
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The Safety and Effectiveness of Interleukin-2 Plus Zidovudine in Patients With AIDS or AIDS Related Complex

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