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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •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-
- •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-
- •Prior Medication:
- •Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study.
排除标准
- •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:
- •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.