Adjuvant Cytokine Therapy to Treat Pulmonary Mycobacterium Avium Complex Infection

Completed · Phase 1

Conditions studied: Mycobacterium Avium-Intracellulare Infection

In brief

Mycobacterium avium complex (MAC) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. With half or more of all patients failing standard three-drug therapy, this is an insidious disease with a poor prognosis. Under the natural history protocol of nontuberculous mycobacterial infection (NTM; #01-I-0202), 46 patients with diagnosed pulmonary MAC disease are being studied. Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection. Cytokines are particularly important in the activaction of macrophages, which help to clear mycobacterial infection. Interferon gamma 1b (Actimmune) and GM-CSF (Leukine) are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution, respectively. A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection. Given the poor outcomes of therapy and the persistent, debilitating nature of the disease, new therapies are desperately needed, and many are being tried without benefit of scientific foundation. Currently, there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously. This protocol proposes to perform a pilot study to evaluate the effects, if any, of these macrophage stimulating cytokines in the context of ongoing pulmonary MAC infection. Aims: To determine the local and systemic effect, if any, of adjuvant IFN gamma and GM-CSF in pulmonary MAC patients. Methods: Fifteen patients will be randomized into three treatment groups of five patients each. The first group will receive a standard drug regimen, based on the 1997 ATS guidelines. The second and third groups, in addition to receiving the standard therapy, will also receive three months of (IFN{gamma}) and GM-CSF, respectively. All patients will undergo bronchoscopy with bronchoalveolar lavage (BAL) at the beginning of the study, after three months, and at six months. In addition to obtaining traditional subjective and objective clinical measures, both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs. In vitro studies on typ...

Key facts

Study ID

NCT00111397

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

2

Starts

2005-05-13

Expected to finish

2010-08-04

Last updated by the study team

2017-07-02

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may not qualify if…

• Patients with pulmonary MAC disease who do not meet the above entry criteria.
• Patients with any of the following preexisting medical conditions:
• HIV positive
• asthma
• active cancer requiring treatment
• hepatic disease (defined as either a history of cirrhosis, or grade 3 or 4 hepatic toxicity by the Toxicity Table in Appendix II of protocol)
• Patients who are unable to tolerate bronchoscopy. This will be defined by the following criteria:
• A pulse oximetry reading less than 100% when given supplemental oxygen at 100% FiO2.
• Clinically significant reactive airway disease that does not respond to bronchodilators.
• Patients with the following laboratory abnormalities:
• creatinine greater than 1.5 mg/dL
• Hemoglobin less than 9 mg/dL
• WBC less than 3,000
• Platelets less than 150,000
• ALT greater than 82 U/L, or AST greater than 78 U/L.
• Bilirubin greater than 2.0 mg/dL
• Alkaline phosphates greater than 232 U/L
• Patients with a preexisting allergy or history of allergic reactions to study or protocol medications. These include, but are not necessarily limited to: IFN-gamma, GM-CSF, azithromycin/ clarithromycin, ethambutol, rifampin/ rifabutin, anesthetic agents employed in bronchoscopy, or any yeast-derived products.
• Patients who are unable to maintain the described follow up schedule. Likewise, patients who are unable to give informed consent are excluded from the study.
• Patients with clinical diagnosis of cystic fibrosis.
• Patients who are either currently smoking, or have a previous history of smoking that exceeds 20 pack years.
• Patients with prior treatment with either IFN-gamma or GM-CSF within the last three months.
• Patients with known history of cardiac, endocrine, neurologic or other medical conditions that the principal investigator deems dangerous or unsuitable for enrollment will be excluded.
• Patients who are either pregnant or lactating. Also, menstruating patients who are randomized to a study group receiving a cytokine and refuse to use appropriate barrier forms of contraception or abstinence during this trial be excluded.
• Patients who, at any time during this trial, have an active lung infection caused by either Staphylococcus or a gram negative rod are excluded from this trial until this infection has been successfully treated.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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