Atypical Mycobacterium Infection Clinical Trial
Official title:
Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections
This study will test the safety and effectiveness of a drug called interleukin-12 (IL-12) in
fighting severe infectious (other than tuberculosis) caused by a group of bacteria called
mycobacteria. IL-12 is similar to a substance the body produces naturally to strengthen
immune function (infection-fighting ability). It works by stimulating white blood cells to
increase production of a chemical called interferon gamma, which can improve or cure
mycobacterial infections in some patients.
In previous studies, IL-12 has improved immune function against mycobacteria in test tube
experiments and in mice. A recent study of three patients with mycobacterial infections
treated with the drug showed encouraging results. The drug has also been studied more
extensively in patients with cancer, HIV infection and hepatitis C.
Patients in this study will receive IL-12 injections under the skin twice a week for one
year. They will be taught how to self-administer the drug, but a home care nurse or a
physician may also give the injections. The drug dosage will be increased each week to
determine the safest and most effective dose for fighting this infection. If intolerable
side effects develop at a certain dose, the previous dose level will be used for the next
injection. That dose will then be used for the rest of the study, unless unacceptable side
effects develop at that level, in which case the dose will again be lowered. Patients will
receive an antibiotic against mycobacteria.
Physical examinations and blood and urine tests will be done once a month for at least the
first year and then every 3 months the following year to evaluate kidney, liver, and immune
function. The first evaluation-at the start of the study-is done on an inpatient basis.
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. ;
Endpoint Classification: Safety Study, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00004296 -
Multicenter Study of Nontuberculous Mycobacteria in Cystic Fibrosis Patients
|
N/A |