HIV InfectionsPhase 1NCT00001005
A Study of Zidovudine Plus Interleukin-2 in HIV-Infected Patients Who Have No Symptoms of Infection But Who Have Tender Lymph Nodes
A Phase 1 study testing Zidovudine and Aldesleukin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
AMENDED: To investigate whether subcutaneous (SC) injection of IL-2 produces biological responses which parallel those observed with IV dosing. Original design: To evaluate the short-term effects of combined administration of zidovudine (AZT) and increasing doses of recombinant interleukin-2 (aldesleukin; IL-2) in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Zidovudine and Aldesleukin
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento Feb 1995
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Necessary topical agents, including nystatin or clotrimazole, as well as acyclovir. Patients on medications without which the patient would be placed at significant risk (seizures, diabetic control, respiratory embarrassment) may continue only at the discretion of the study pharmacologist.
- Patients must have:
- Asymptomatic HIV infection associated with lymphadenopathy.
- Walter Reed Stage II disease, with positive antibody to HIV confirmed by Western blot test.
Who cannot join
- Co-existing Condition:
- Patients will be excluded from the study for the following:
- Development of a disease requiring a drug which might potentiate toxicity of the study drugs or a drug likely to have antiretroviral effect.
- Active opportunistic infection.
- Major organ allograft.
- Significant cardiac or pulmonary disease or central nervous system (CNS) lesions.
Show all 21Show fewer
- Concurrent Medication:
- Excluded:
- Ongoing therapy for an opportunistic infection.
- Beta-blockers.
- Antihypertensive medication other than diuretics.
- All nonessential medication including pain medications.
- Patients without interleukin 2 (IL-2) augmentable anti-HIV antibody-dependent cellular cytotoxicity (ADCC) or or cell-mediated cytotoxicity (CMC) in vitro are excluded.
- Prior Medication:
- Excluded within 12 weeks of study entry:
- Other antiretroviral agents (patients with CD4 counts of 400 - 500 per mm3 who are receiving AZT may continue to receive it until study treatment is initiated).
- Immunomodulators.
- Corticosteroids.
- Other experimental therapy.
- Antineoplastic chemotherapy.
- Active drug or alcohol abuse.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
About this study
Official title: Interleukin-2 Augmentation of Specific Anti-HIV Immune Responses: Phase I Trial of the Combination of 3'-Azido-3'-Deoxythymidine (Zidovudine) and Recombinant Interleukin-2 in Patients With Asymptomatic HIV Infection Associated With Lymphadenopathy (Walter Reed Stage II)
AMENDED: To investigate whether subcutaneous (SC) injection of IL-2 produces biological responses which parallel those observed with IV dosing. Original design: To evaluate the short-term effects of combined administration of zidovudine (AZT) and increasing doses of recombinant interleukin-2 (aldesleukin; IL-2) in patients infected with HIV, who have lymphadenopathy, but who are otherwise asymptomatic (no other symptoms). The first phase of this clinical trial will establish maximum tolerated dose ( MTD ). How quickly the drugs get into the blood and how long they remain there (pharmacokinetics) will also be studied at each dose as well as the effect on HIV.
Since AZT has no effect on cells that contain inactive virus (latently infected cells) and these cells may act as viral reservoirs, that a second agent that can destroy these infected cells would be useful in combination with AZT. The different activities of AZT and IL-2, as well as the non-overlapping nature of their mechanisms of action and toxicity, increase the theoretical benefits of combining AZT, a drug which has clinically significant activity in HIV-related disease but cannot eliminate infected cells, with IL-2, a drug which may enhance anti-HIV immunity, destroy chronically infected cells, and allow immune recognition of latently infected cells.
Read the detailed description
Since AZT has no effect on cells that contain inactive virus (latently infected cells) and these cells may act as viral reservoirs, that a second agent that can destroy these infected cells would be useful in combination with AZT. The different activities of AZT and IL-2, as well as the non-overlapping nature of their mechanisms of action and toxicity, increase the theoretical benefits of combining AZT, a drug which has clinically significant activity in HIV-related disease but cannot eliminate infected cells, with IL-2, a drug which may enhance anti-HIV immunity, destroy chronically infected cells, and allow immune recognition of latently infected cells.
Five patients who have already received and tolerated oral AZT for at least 8 weeks continue their AZT treatment and at the same time receive IL-2 on a schedule of 5 days on the drug, 2 days off the drug. The IL-2 is administered by 30-minute intravenous (IV) infusion according to this schedule for 4 weeks. The first week of IL-2 treatment is on an inpatient basis and the remaining 3 weeks are on an outpatient basis. Toxicity is monitored every week. Maximum tolerated dose (MTD) is defined as the maximum dose at which 3 out of 5 patients experience Grade 3 or above toxicity during the course of IL-2 administration. A second cohort of five patients will receive IV IL-2. If the MTD is not reached, five additional patients will receive IV IL-2. All five patients in a given cohort must complete a full 4-week course of IL-2 before subsequent patients are entered at the next higher dose level. After IV dosing is completed at these three levels, additional 5-patient cohorts receive subcutaneous (SC) IL-2 according to the same schedule. Each patient is restricted to one dosage group. Patients are treated and followed for a total of 24 weeks. Patients receive ibuprofen for fever and chills.
- Conditions
- HIV Infections
- Being tested
- Zidovudine, Aldesleukin
- Keywords
- Recombinant Proteins, HIV Seropositivity, Interleukin-2, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
- Medical subject headings
- HIV Infections, HIV Seropositivity, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZidovudineDrug
AldesleukinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionFeb 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- K Weinhold, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001005
- Sponsor's protocol ID
- ACTG 042
- Other IDs
- 11017
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Weinhold K, Tyler D, Austin A, Lyerly K, Bolognesi D, Bartlett J. Augmentation of non-mhc restricted cellular cytotoxicities in patients receiving Zidovudine plus interleukin 2. Int Conf AIDS. 1989 Jun 4-9;5:406 (abstract no WBP330)
Bartlett JA, Blankenship KD, Greenberg M, Tyler DS, Weinhold KJ. The safety of Zidovudine and interleukin 2 in asymptomatic HIV infected patients. Int Conf AIDS. 1989 Jun 4-9;5:406 (abstract no WBP325)
Bartlett JA, Berend C, Petroni GR, Ottinger J, Tyler DL, Pettinelli C, Weinhold KJ. Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042. J Infect Dis. 1998 Oct;178(4):1170-3. doi: 10.1086/515677.
PubMed 9806053
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interleukin-2 Augmentation of Specific Anti-HIV Immune Responses: Phase I Trial of the Combination of 3'-Azido-3'-Deoxythymidine (Zidovudine) and Recombinant Interleukin-2 in Patients With Asymptomatic HIV Infection Associated With Lymphadenopathy (Walter Reed Stage II)
- ClinicalTrials.gov ID
- NCT00001005
- Acronym / sponsor ID
- ACTG 042
- Conditions
- HIV Infections
- Keywords
- Recombinant Proteins, HIV Seropositivity, Interleukin-2, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Feb 1995 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AMENDED: To investigate whether subcutaneous (SC) injection of IL-2 produces biological responses which parallel those observed with IV dosing. Original design: To evaluate the short-term effects of combined administration of zidovudine (AZT) and increasing doses of recombinant interleukin-2 (aldesleukin; IL-2) in patients infected with HIV, who have lymphadenopathy, but who are otherwise asymptomatic (no other symptoms). The first phase of this clinical trial will establish maximum tolerated dose ( MTD ). How quickly the drugs get into the blood and how long they remain there (pharmacokinetics) will also be studied at each dose as well as the effect on HIV.
Since AZT has no effect on cells that contain inactive virus (latently infected cells) and these cells may act as viral reservoirs, that a second agent that can destroy these infected cells would be useful in combination with AZT. The different activities of AZT and IL-2, as well as the non-overlapping nature of their mechanisms of action and toxicity, increase the theoretical benefits of combining AZT, a drug which has clinically significant activity in HIV-related disease but cannot eliminate infected cells, with IL-2, a drug which may enhance anti-HIV immunity, destroy chronically infected cells, and allow immune recognition of latently infected cells.
Detailed description
Since AZT has no effect on cells that contain inactive virus (latently infected cells) and these cells may act as viral reservoirs, that a second agent that can destroy these infected cells would be useful in combination with AZT. The different activities of AZT and IL-2, as well as the non-overlapping nature of their mechanisms of action and toxicity, increase the theoretical benefits of combining AZT, a drug which has clinically significant activity in HIV-related disease but cannot eliminate infected cells, with IL-2, a drug which may enhance anti-HIV immunity, destroy chronically infected cells, and allow immune recognition of latently infected cells.
Five patients who have already received and tolerated oral AZT for at least 8 weeks continue their AZT treatment and at the same time receive IL-2 on a schedule of 5 days on the drug, 2 days off the drug. The IL-2 is administered by 30-minute intravenous (IV) infusion according to this schedule for 4 weeks. The first week of IL-2 treatment is on an inpatient basis and the remaining 3 weeks are on an outpatient basis. Toxicity is monitored every week. Maximum tolerated dose (MTD) is defined as the maximum dose at which 3 out of 5 patients experience Grade 3 or above toxicity during the course of IL-2 administration. A second cohort of five patients will receive IV IL-2. If the MTD is not reached, five additional patients will receive IV IL-2. All five patients in a given cohort must complete a full 4-week course of IL-2 before subsequent patients are entered at the next higher dose level. After IV dosing is completed at these three levels, additional 5-patient cohorts receive subcutaneous (SC) IL-2 according to the same schedule. Each patient is restricted to one dosage group. Patients are treated and followed for a total of 24 weeks. Patients receive ibuprofen for fever and chills.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Necessary topical agents, including nystatin or clotrimazole, as well as acyclovir. Patients on medications without which the patient would be placed at significant risk (seizures, diabetic control, respiratory embarrassment) may continue only at the discretion of the study pharmacologist.
- Asymptomatic HIV infection associated with lymphadenopathy.
- Walter Reed Stage II disease, with positive antibody to HIV confirmed by Western blot test.
Key exclusion criteria (21 listed)
- Development of a disease requiring a drug which might potentiate toxicity of the study drugs or a drug likely to have antiretroviral effect.
- Active opportunistic infection.
- Major organ allograft.
- Significant cardiac or pulmonary disease or central nervous system (CNS) lesions.
- Ongoing therapy for an opportunistic infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zidovudine | Drug | – |
| Aldesleukin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- BackgroundWeinhold K, Tyler D, Austin A, Lyerly K, Bolognesi D, Bartlett J. Augmentation of non-mhc restricted cellular cytotoxicities in patients receiving Zidovudine plus interleukin 2. Int Conf AIDS. 1989 Jun 4-9;5:406 (abstract no WBP330)
- BackgroundBartlett JA, Blankenship KD, Greenberg M, Tyler DS, Weinhold KJ. The safety of Zidovudine and interleukin 2 in asymptomatic HIV infected patients. Int Conf AIDS. 1989 Jun 4-9;5:406 (abstract no WBP325)
- Background: PubMed 9806053Bartlett JA, Berend C, Petroni GR, Ottinger J, Tyler DL, Pettinelli C, Weinhold KJ. Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042. J Infect Dis. 1998 Oct;178(4):1170-3. doi: 10.1086/515677.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
K Weinhold study chair
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zidovudine and Aldesleukin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001005, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.