HIV InfectionsPhase 1NCT00000899
A Study on the Effect of Chemotherapy Combined With Anti-HIV Drugs in HIV-Positive Patients
A Phase 1 study testing Nelfinavir mesylate, Lamivudine and Filgrastim in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
The purpose of this study is to determine the safety of anti-HIV drugs combined with low-dose chemotherapy (consisting of cyclophosphamide [CTX]) in HIV-positive patients. This study examines whether this combination therapy can reduce the number of HIV-infected cells hidden in the lymph nodes and blood. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Nelfinavir mesylate, Lamivudine and Filgrastim
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Start not givento Oct 2001
- 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 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- You may be eligible for this study if you:
- Are HIV-positive.
- Have a CD4 count above 300 cells/mm3 within 30 days of study entry.
- Have an HIV viral load between 10,000 and 200,000 copies/ml.
- Are between the ages of 18 and 50.
- Agree to practice abstinence or to use a barrier method of birth control during the study (such as condoms).
Who cannot join
- You may not be eligible for this study if you:
- Have had cancer requiring chemotherapy or radiotherapy or certain nervous system diseases.
- Are sensitive to E. coli-derived proteins.
- Have an active AIDS-defining illness.
- Require certain medications.
- Are pregnant or breast-feeding.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Univ of North Carolina
Chapel Hill, North Carolina, 275997215
Duke Univ Med Ctr
Durham, North Carolina, 27710
About this study
Official title: Effect of Cytoreductive Chemotherapy Combined With Highly Active Antiretroviral Therapy on Lymph Node HIV DNA in HIV-Infected Subjects
The purpose of this study is to determine the safety of anti-HIV drugs combined with low-dose chemotherapy (consisting of cyclophosphamide [CTX]) in HIV-positive patients. This study examines whether this combination therapy can reduce the number of HIV-infected cells hidden in the lymph nodes and blood.
Current anti-HIV drug treatments can greatly reduce the levels of HIV in the human body. However, HIV can hide in certain immune cells and escape the drugs' effects. Chemotherapy using CTX destroys these immune cells. When used with standard anti-HIV drug treatments, CTX may be able to speed up the elimination of HIV-infected cells.
Read the detailed description
HAART is a potent suppressor of plasma and lymph node HIV RNA. However, studies suggest that HAART cannot significantly diminish reservoirs of chronically HIV-infected cells. Strategies designed to eradicate all HIV infection should seek to actively target these reservoirs. CTX administration has been shown to eliminate a large number of lymphoid tissue T cells and macrophages, appearing to actively target chronically HIV-infected cells. As lymphoid organs are repopulated following initial depletion with CTX, HAART may protect repopulating cells from becoming HIV-infected, resulting in a net additional removal of the HIV-infected lymphoid reservoir.
In Step 1 of this 2-step protocol, all patients receive a HAART regimen of nelfinavir (NFV) plus stavudine (d4T) plus lamivudine (3TC). Patients who achieve an acceptable virologic response, defined as 2 consecutive HIV RNA determinations below 500 copies/ml at least 2 weeks apart between Weeks 4 and 16 of Step 1 [AS PER AMENDMENT 10/30/98: defined as 2 consecutive plasma HIV RNA determinations below 50 copies/ml by the Roche Ultrasensitive assay within a 4-week period between Weeks 4 and 24], are randomized to Arm A or B of Step 2. In Arm A, patients receive NFV plus d4T plus 3TC. In Arm B, patients receive NFV plus d4T plus 3TC plus 3 escalating doses of CTX at 6-week intervals. Patients in both arms are followed for at least 52 weeks following randomization to Step 2. During this time, patients undergo blood tests and lymph node biopsies to measure HIV DNA and RNA levels and to characterize the T cell population. Additionally, patients undergo a chest CT of the thymus before randomization to Step 2 and at Week 52 of Step 2. Cerebrospinal fluid may be obtained at Week 52 to determine the amount of HIV RNA and DNA present. [AS PER AMENDMENT 10/30/98: G-CSF is given after the first dose of CTX, at the discretion of the investigator, and after the second and third doses, for up to 14 days, until the absolute neutrophil count is 10,000 cells/mm3. Also, CTX doses may be modified based on pharmacokinetic study results.]
- Conditions
- HIV Infections
- Being tested
- Nelfinavir mesylate, Lamivudine, Filgrastim, Stavudine, Cyclophosphamide
- Keywords
- Cyclophosphamide, Dose-Response Relationship, Drug, Drug Therapy, Combination, Granulocyte Colony-Stimulating Factor, Combined Modality Therapy, Antineoplastic Agents, Lymph Nodes, Stavudine, HIV Protease Inhibitors, Lamivudine, DNA, Viral, RNA, Viral, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Nelfinavir, Antineoplastic Agents, Alkylating
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nelfinavir mesylateDrug
LamivudineDrug
FilgrastimDrug
StavudineDrug
CyclophosphamideDrug
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 completionOct 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Enrolment
- 10 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John A. Bartlett, MD, Study chair, Duke Univ Med Ctr
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000899
- Sponsor's protocol ID
- ACTG 380
- Other IDs
- 11341
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 29 Oct 2021
- Results posted
- No
Publications
Bartlett JA, Silberman M, Miralles GD, Sevin A, Pruitt S, Ottinger J, Gryszowka V, Fiscus S, Bucy BP. Antiretroviral therapy (ART) plus cyclophosphamide (CTX) to diminish HIV DNA in lymphoid tissue. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 16)
Bartlett JA, Miralles GD, Sevin AD, Silberman M, Pruitt SK, Ottinger J, Gryszowska V, Fiscus SA, Bucy RP; ACTG 380 Study Team. Addition of cyclophosphamide to antiretroviral therapy does not diminish the cellular reservoir in HIV-infected persons. AIDS Res Hum Retroviruses. 2002 May 20;18(8):535-43. doi: 10.1089/088922202753747888.
PubMed 12036483
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cytoreductive Chemotherapy Combined With Highly Active Antiretroviral Therapy on Lymph Node HIV DNA in HIV-Infected Subjects
- ClinicalTrials.gov ID
- NCT00000899
- Acronym / sponsor ID
- ACTG 380
- Conditions
- HIV Infections
- Keywords
- Cyclophosphamide, Dose-Response Relationship, Drug, Drug Therapy, Combination, Granulocyte Colony-Stimulating Factor, Combined Modality Therapy, Antineoplastic Agents, Lymph Nodes, Stavudine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Oct 2001 (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.
The purpose of this study is to determine the safety of anti-HIV drugs combined with low-dose chemotherapy (consisting of cyclophosphamide [CTX]) in HIV-positive patients. This study examines whether this combination therapy can reduce the number of HIV-infected cells hidden in the lymph nodes and blood.
Current anti-HIV drug treatments can greatly reduce the levels of HIV in the human body. However, HIV can hide in certain immune cells and escape the drugs' effects. Chemotherapy using CTX destroys these immune cells. When used with standard anti-HIV drug treatments, CTX may be able to speed up the elimination of HIV-infected cells.
Detailed description
HAART is a potent suppressor of plasma and lymph node HIV RNA. However, studies suggest that HAART cannot significantly diminish reservoirs of chronically HIV-infected cells. Strategies designed to eradicate all HIV infection should seek to actively target these reservoirs. CTX administration has been shown to eliminate a large number of lymphoid tissue T cells and macrophages, appearing to actively target chronically HIV-infected cells. As lymphoid organs are repopulated following initial depletion with CTX, HAART may protect repopulating cells from becoming HIV-infected, resulting in a net additional removal of the HIV-infected lymphoid reservoir.
In Step 1 of this 2-step protocol, all patients receive a HAART regimen of nelfinavir (NFV) plus stavudine (d4T) plus lamivudine (3TC). Patients who achieve an acceptable virologic response, defined as 2 consecutive HIV RNA determinations below 500 copies/ml at least 2 weeks apart between Weeks 4 and 16 of Step 1 [AS PER AMENDMENT 10/30/98: defined as 2 consecutive plasma HIV RNA determinations below 50 copies/ml by the Roche Ultrasensitive assay within a 4-week period between Weeks 4 and 24], are randomized to Arm A or B of Step 2. In Arm A, patients receive NFV plus d4T plus 3TC. In Arm B, patients receive NFV plus d4T plus 3TC plus 3 escalating doses of CTX at 6-week intervals. Patients in both arms are followed for at least 52 weeks following randomization to Step 2. During this time, patients undergo blood tests and lymph node biopsies to measure HIV DNA and RNA levels and to characterize the T cell population. Additionally, patients undergo a chest CT of the thymus before randomization to Step 2 and at Week 52 of Step 2. Cerebrospinal fluid may be obtained at Week 52 to determine the amount of HIV RNA and DNA present. [AS PER AMENDMENT 10/30/98: G-CSF is given after the first dose of CTX, at the discretion of the investigator, and after the second and third doses, for up to 14 days, until the absolute neutrophil count is 10,000 cells/mm3. Also, CTX doses may be modified based on pharmacokinetic study results.]
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Are HIV-positive.
- Have a CD4 count above 300 cells/mm3 within 30 days of study entry.
- Have an HIV viral load between 10,000 and 200,000 copies/ml.
- Are between the ages of 18 and 50.
- Agree to practice abstinence or to use a barrier method of birth control during the study (such as condoms).
Key exclusion criteria (6 listed)
- Have had cancer requiring chemotherapy or radiotherapy or certain nervous system diseases.
- Are sensitive to E. coli-derived proteins.
- Have an active AIDS-defining illness.
- Require certain medications.
- Are pregnant or breast-feeding.
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 |
|---|---|---|
| Nelfinavir mesylate | Drug | – |
| Lamivudine | Drug | – |
| Filgrastim | Drug | – |
| Stavudine | Drug | – |
| Cyclophosphamide | 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 29 Oct 2021.
- BackgroundBartlett JA, Silberman M, Miralles GD, Sevin A, Pruitt S, Ottinger J, Gryszowka V, Fiscus S, Bucy BP. Antiretroviral therapy (ART) plus cyclophosphamide (CTX) to diminish HIV DNA in lymphoid tissue. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 16)
- Background: PubMed 12036483Bartlett JA, Miralles GD, Sevin AD, Silberman M, Pruitt SK, Ottinger J, Gryszowska V, Fiscus SA, Bucy RP; ACTG 380 Study Team. Addition of cyclophosphamide to antiretroviral therapy does not diminish the cellular reservoir in HIV-infected persons. AIDS Res Hum Retroviruses. 2002 May 20;18(8):535-43. doi: 10.1089/088922202753747888.
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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.
John A. Bartlett, MD study chair
Duke Univ Med Ctr
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nelfinavir mesylate, Lamivudine and Filgrastim in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 6 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 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 NCT00000899, which also lists 2 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 29 Oct 2021.