Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections

NCT00001911 | Completed Phase 1

• 2 other identifiers: 99014799-I-0147
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atypical Mycobacterium Infection

Keywords

Cytokine; Interferon Gamma; Pulmonary; Disseminated; Refractory; Mycobacterial Infection; Nontuberculosis Mycobacterial Infection; Pulmonary Nontuberculous Mycobacterial Infection

Interventions

Interleukin-12 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998 May 29;280(5368):1432-5. doi: 10.1126/science.280.5368.1432.

  PMID: 9603732 BACKGROUND

• Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova JL, Kumararatne DS. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest. 1998 Dec 15;102(12):2035-40. doi: 10.1172/JCI4950.

  PMID: 9854038 BACKGROUND

• Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M, Young HA, Wolf SF, Young D, Clark SC, Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869-79. doi: 10.1084/jem.173.4.869.

  PMID: 1672545 BACKGROUND

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections

Interventions

Interleukin-12

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: July 1, 1999
• Study Completion: July 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-07

Locations

US (1)