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A Study on the Effect of Chemotherapy Combined With Anti-HIV Drugs in HIV-Positive Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000899
First received: November 2, 1999
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Nelfinavir mesylate
Drug: Lamivudine
Drug: Filgrastim
Drug: Stavudine
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: Effect of Cytoreductive Chemotherapy Combined With Highly Active Antiretroviral Therapy on Lymph Node HIV DNA in HIV-Infected Subjects

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 10
Study Completion Date: October 2001
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.]

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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).

Exclusion Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000899

Locations
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Investigators
Study Chair: John A. Bartlett, MD Duke Univ Med Ctr
  More Information

Additional Information:
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000899     History of Changes
Other Study ID Numbers: ACTG 380, 11341
Study First Received: November 2, 1999
Last Updated: February 16, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Cyclophosphamide
Lamivudine
Nelfinavir
Reverse Transcriptase Inhibitors
Stavudine
Alkylating Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antirheumatic Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 20, 2014