Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections
Interleukin-12
Actinomycetales Infections+4
+ Bacterial Infections and Mycoses
+ Bacterial Infections
Treatment Study
Summary
Study start date: July 1, 1999
Actual date on which the first participant was enrolled.Severe nontuberculous mycobacterial infections in patients who are not infected with HIV have been shown to be due to abnormalities in the pathways that generate or use interferon gamma (IFN gamma). In some of these patients treatment with IFN gamma has been effective in improving or curing these infections. Recently, interleukin-12 (IL-12) has been shown to be a potent inducer of IFN gamma along with other cytokines. Experiments in animals and preliminary experience by us in humans suggests that IL-12 may be an important adjunct to antimycobacterial therapy. We seek to use IL-12 in a phase I/II trial in the treatment of severe nontuberculous mycobacterial infections in patients who have not been cured by the best tolerated conventional therapy with IFN gamma. Patients will be studied for inborn or acquired immune defects as well as IL-12 responsiveness in vitro under protocol 93-I-0119 "Detection and Characterization of Host Defense Defects". Patients will receive IL-12 subcutaneously 2 times weekly. We will use an intrapatient dose escalation protocol ranging from 20 ng/kg to 300 ng/kg, depending on the highest dose tolerated by the patient. We expect this study to yield valuable information about tolerance and toxicity. We seek to treat 10 patients over the next 3 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.10 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Severe disseminated or pulmonary nontuberculous mycobacterial infection refractory to the best tolerated conventional therapy in addition to IFN gamma delivered for at least 3 months. This infection must have been proven by culture at some point during the illness. At the time of enrollment, patients will be eligible if they have negative cultures but histopathologic, examinable, or radiographic evidence of ongoing infection. In vitro responsiveness to IL-12 as demonstrated by augmentation of peripheral blood mononuclear cell (PBMC) phytohemagglutinin (PHA) induced IFN gamma production. Women of childbearing age must have a negative pregnancy test (urine or serum) at the time of starting the study and agree to take measures to avoid pregnancy throughout the study while receiving IL-12. Males will be advised that the effects of IL-12 on sperm are not well-known, and they should avoid conception during the study period. Age 18 years or over. Adequate hematopoietic, renal and hepatic function, defined as: Absolute neutrophil count greater than or equal to 1000/microL (G-CSF permitted); Hemoglobin greater than or equal to 9 g/dl (transfusion or erythropoietin permitted); Platelet count greater than or equal to 100,000/microL; Creatinine less than or equal to 1.5 X upper limit of normal; Bilirubin less than or equal to 1.5 X upper limit of normal; AST/SGOT less than or equal to 2.5 X upper limit of normal; ALT/SGPT less than or equal to 2.5 X upper limit of normal; Calculated Creatinine Clearance greater than 60 mL/min. Karnofsky Performance Status index greater than or equal to 70. Written signed informed consent. No HIV infection. No active malignancy. No symptomatic cardiac disease or ongoing treatment for same. No active seizure disorder or ongoing treatment for same. No pregnancy or lactation. No surgery during the two weeks prior to the start of IL-12. No concurrent use of systematic corticosteroids, except for physiologic replacement. No exposure to any investigational drug within four weeks prior to the start of dosing. No gastrointestinal bleeding or uncontrolled peptic ulcer disease. No history of inflammatory bowel disease or autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus. No other major illness which, in the investigator's judgement, will substantially increase the risk associated with the patient's participation in this study.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOpen National Institute of Allergy and Infectious Diseases (NIAID) in Google Maps