This study will determine what dose of recombinant interferon-gamma is safe and effective
for treating multiple drug-resistant tuberculosis. Recombinant interferon-gamma is a
genetically engineered form of a substance normally produced by the body and is used to
boost immune function.
Patients 5 years of age and older with multiply drug-resistant tuberculosis may be eligible
for this study.
Participants will be admitted to either the NIH Clinical Center in Bethesda, Maryland, the
Texas Center for Infectious Diseases in San Antonio or the South Texas Hospital or Valley
Baptist Hospital, both in Harlingen, Texas. On admission, patients will have a medical
history, physical examination, blood and urine tests, sputum culture, X-rays, pulmonary
function tests and a computed tomography (CT) scan. CT produces 3-dimensional images of body
tissues and organs in small sections. For the procedure, the patient lies still on a table
surrounded by the scanner.
All patients will continue treatment with anti-tuberculosis antibiotics during and after the
study period and may elect whether or not to take gamma interferon in addition to the
antibiotic. Five patients will receive only antibiotic treatment, and 5 each will receive
one of 3 doses (0.025, 0.05 or 0.1 milligrams per square meter of body surface area) of
interferon-gamma injected under the skin 3 times a week. The patient or caregiver will be
taught to give the injections, which are similar to insulin injections for diabetes.
Patients will be in isolation in the hospital from the start of therapy until sputum samples
show no evidence of tuberculosis for 3 consecutive weeks. Following that, they will repeat
the tests done on admission (except CT) during follow-up visits (1- to 2-day
hospitalizations) at 3, 6, 9, 12, 15, 18 and 24 months after the start of therapy. Patients
taking interferon gamma will have blood drawn more frequently (monthly) for the first 6
months, and patients with lung infection will have sputum samples collected more
frequently-weekly for the first 3 months or until three consecutive negative samples are
obtained and then monthly throughout the course of therapy. Patients with lung infection
will also have repeat CT scans at 6 and 12 months while on interferon gamma. In one or two
patients on the drug, blood will be drawn frequently following one injection of gamma
interferon (just before the injection and again at 0.25, 0.5, 1, 6, 12, 18, 24 and 48 hours
after it) to see if a difference in blood levels of the drug can be detected.
This is a phase I/II, controlled, open label, dose escalation study to determine the
tolerance, toxicity, and clinical effect of the administration of interferon-gamma on the
clinical condition and immune function of patients with multiply drug resistant M.
tuberculosis infections (MDRTB). The study drug (interferon gamma) will be administered
subcutaneously three times a week at three dose levels (0.025 mg/m(2), 0.05 mg/m(2), 0.1
mg/m(2)) for one year in addition to anti-tuberculous medications, as determined by in vitro
Clinical and microbiologic/histologic demonstration of MDRTB, either disseminated (i.e.
infection at 2 or more non-contiguous sites) or pulmonary.
Preserved renal function (creatinine less than or equal to 2 mg/100 ml; less than or equal
to 2+ proteinuria).
Preserved hepatic function (bilirubin less than or equal to 1.5 mg/100 ml; prothrombin
time less than or equal to 1.3x control).
Preserved hematologic function (WBC greater than or equal to 3000/mm3; granulocytes
greater than 1500/mm3; platelets greater than or equal to 100,000/mm3).
Patients of childbearing potential may be entered if using effective contraception and
having a negative serum or urine HCG within one week of beginning therapy.
Presence of causes of secondary immunodeficiency such as HIV or malignancy.
Currently receiving cytotoxic therapy, or have received it within the last 3 months.
Pregnant or lactating women may not be entered.
Patients with a known seizure disorder may not be entered.
Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery
disease may not be entered.
Patients unable, in the judgment of the PI, to comply with the treatment regimen will be