Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections

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.