Clinical trial NCT00001112: The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Monocytes
Interferon-gamma, Recombinant
Injections, Subcutaneous
Immune System
Drug Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Blood Bactericidal Activity
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Cornell University A2201
state: New York
Study officials:
name: HW Murray
role: STUDY_CHAIR
References:
citation: Murray HW, Scavuzzo D, Jacobs JL, Kaplan MH, Libby DM, Schindler J, Roberts RB. In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. J Immunol. 1987 Apr 15;138(8):2457-62.