The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001112
First received: November 2, 1999
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

To find out which of four doses of (recombinant) human interferon gamma (IFN-G) is most effective in stimulating the white blood cells (monocytes) to fight infection and to see if treatment with IFN-G can strengthen the ability of AIDS patients to control infections. This study will also determine how long after a single injection of IFN-G white blood cells remain stimulated.

AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Interferon gamma-1b
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study To Determine the Safety of the Optimal Monocyte Activating Administration Schedule of Subcutaneous Human Recombinant Interferon-gamma in ZDV-Treated Patients With AIDS

Resource links provided by NLM:


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

Estimated Enrollment: 5
Study Completion Date: April 1993
Detailed Description:

AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best.

Patients, who may participate in all three parts of the study, are maintained on a stable dose of AZT. In part A (optimal dose), five AIDS patients who have had an AIDS related opportunistic infection receive 4 once-weekly increasing doses of IFN-G. Monocyte antimicrobial activity is examined in test tube studies before and after each injection of IFN-G. In part B, five patients receive the optimal dose of IFN-G established in part A. Patients enrolled from part A have completed at least 2 weeks of part A before enrolling in part B. Antimicrobial activity is examined 1, 2, and 3 days after a single injection of the optimal dose of IFN-G (determined in part A). In part C (safety and tolerance of combined treatment of IFN-G and AZT), patients are treated with IFN-G for 4 weeks using the optimal dose and administration schedule derived from parts A and B.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Prophylactic antibiotics.
  • Tylenol (650 mg orally every 6 hours as needed for temperature > 38.5 degrees C).
  • Meperidine (25 - 50 mg intravenously, once, for severe rigors if systolic blood pressure is > 90 mmHg).

Patients must meet criteria for AIDS classification (CDC) category IV C-1.

  • Patients must have had one or more prior opportunistic infections identified in surveillance definition of AIDS. Patients whose AIDS-defining illness is Kaposi's sarcoma are also eligible if they have previously had one of the secondary infectious diseases identified in category C-1.

Prior Medication:

Required:

  • Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment.
  • Presence of an active opportunistic infection that requires treatment.
  • Hemorrhagic diathesis or active bleeding disorder.
  • Clinically apparent vascular disease.

Concurrent Medication:

Excluded:

  • Medications required for treatment of active cardiac disease.
  • Ongoing therapy with anticoagulants or thrombolytic agents.

Patients with the following are excluded:

  • Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment.
  • Presence of an active opportunistic infection that requires treatment.
  • Hemorrhagic diathesis or active bleeding disorder.
  • Clinically apparent vascular disease.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Antiviral chemotherapy other than zidovudine.
  • Excluded within 12 weeks of study entry:
  • Immunosuppressive or cytotoxic therapy.
  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: NCT00001112

Locations
United States, New York
Cornell University A2201
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Study Chair: HW Murray
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001112     History of Changes
Other Study ID Numbers: ACTG 072, 11046
Study First Received: November 2, 1999
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Monocytes
Interferon-gamma, Recombinant
Injections, Subcutaneous
Immune System
Drug Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Blood Bactericidal Activity

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Interferons
Zidovudine
Interferon-gamma
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 29, 2014