Advertisement

Topics

Daclizumab to Treat Wegener's Granulomatosis

2014-08-27 03:55:59 | BioPortfolio

Summary

This study will examine the safety and effectiveness of daclizumab (also called Zenapax or anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis can affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Standard treatment is a combination of prednisone and a cytotoxic agent (a drug that interferes with cell growth), usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will focus on the effectiveness of daclizumab in preventing disease relapse.

The Food and Drug Administration approved daclizumab in 1997 for preventing kidney transplant rejection, and the drug has also been studied in people with an eye infection called uveitis. The drug works by binding to a protein on T lymphocytes (white blood cells of the immune system) called CD25. This prevents another protein, called interleukin-2, from binding to this site, thereby preventing a series of events that normally results in inflammation.

Patients between 10 and 75 years of age with Wegener's granulomatosis may be eligible for this study.

Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, x-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be conducted. All patients will begin treatment with prednisone and cyclophosphamide daily. Those who improve on this regimen will reduce the prednisone gradually and continue with cyclophosphamide until their disease is in remission. While taking cyclophosphamide, patients must have blood and urine tests done every 1 to 2 weeks. Those who achieve disease remission will stop cyclophosphamide and start taking methotrexate once a week, usually by mouth but possibly by injection into the muscle or skin. Blood and urine tests will be conducted once a week for 4 weeks while the dosage is being adjusted and then once a month for the duration of treatment. Patients on methotrexate whose prednisone dose is reduced to 10 to 30 mg every other day will be randomly assigned either to receive or not receive daclizumab in addition to the methotrexate. Daclizumab is given intravenously (through a plastic tube inserted into a vein) the day after the randomization, then again in 2 weeks, 4 weeks, and once a month for 18 months.

All patients will continue to taper their prednisone dose until it is stopped. Methotrexate will continue for 2 years. Patients whose disease remains in remission at this time will decrease the methotrexate dose. If there is no active disease when both prednisone and methotrexate have been stopped, no further treatment will be given. If disease recurs at a later time, treatment will be reinstituted. The treatment will be determined by the severity of disease, other medical conditions, and history of side effects. Patients not randomized to daclizumab who relapse while still taking methotrexate may be offered re-treatment with daclizumab.

Patients will be evaluated in the outpatient clinic every 4 to 8 weeks until randomization. Patients not taking daclizumab will be followed every 4 to 12 weeks; those taking the drug will be seen every 2 weeks for the first month, every month after that during the 18-month treatment period, and every 4 to 12 weeks until all medications stop. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.

Description

The purpose of this study is to assess the safety and efficacy of daclizumab as an adjunctive treatment to methotrexate in maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will receive methotrexate for remission maintenance. Following the switch to methotrexate and when the prednisone dose has been tapered to 20mg QOD (plus or minus 10mg QOD), patients in remission will be randomized to receive daclizumab or not receive daclizumab. Those randomized to receive daclizumab will be treated with 1 mg/kg intravenously on day 0, week 2, week 4 and every month thereafter for a total of 18 months (20 doses). Regardless to which arm the patient is randomized, they will continue to receive methotrexate. Two years after the methotrexate was started, if the patient remains in remission, this will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events.

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Conditions

Wegener's Granulomatosis

Intervention

Daclizumab

Location

National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda
Maryland
United States
20892

Status

Completed

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:55:59-0400

Clinical Trials [93 Associated Clinical Trials listed on BioPortfolio]

Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis

Wegener's granulomatosis (WG) is a rare disease that causes inflammation of blood vessels, or vasculitis. It may involve many different parts of the body, but typically affects the upper a...

Phase I Trial of Recombinant Human Interleukin-10 (SCH 52000) in Patients With Wegener's Granulomatosis

The purpose of this study is to assess the safety, tolerance, and immunologic effects of interleukin-10 (IL-10), in patients with Wegener's granulomatosis. A secondary objective is to det...

Treatment of Wegener's Granulomatosis With Cyclophosphamide

The purpose of this protocol is to continue to treat patients with Wegener's granulomatosis who have already entered the study, and to treat new patients. The investigators will attempt t...

Etanercept for Wegener's Granulomatosis

This study will determine if the drug etanercept, also called Enbrel, is effective in producing and maintaining remission (reduction of disease symptoms) of Wegener's granulomatosis (WG). ...

Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis

This is a phase IV, single-center, randomized, placebo-controlled pilot study that will evaluate the efficacy of rituximab at inducing otolaryngologic remission in GPA patients with active...

PubMed Articles [55 Associated PubMed Articles listed on BioPortfolio]

Mycophenolate mofetil for induction and maintenance of remission in naïve patients with granulomatosis with polyangiitis without renal involvement.

Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides include granulomatosis with polyangiitis (GPA, previously called Wegener's), microscopic polyangiitis (MPA) and eosinophilic granul...

Reconstruction of Wegener Granulomatosis Nose Deformity Using Fascia Lata Graft.

Wegener granulomatosis (WG) is a necrotizing vasculitis that involves the upper respiratory tract, the lungs, and the kidneys. It also causes deformities of the nose in practically all patients, alter...

Granulomatosis with Polyangiitis (Wegener's Granulomatosis): Evolving Concepts in Treatment.

Granulomatosis with polyangiitis (GPA), formerly termed , is the most common of the pulmonary vasculitides. GPA typically involves the upper respiratory tract, lower respiratory tract (bronchi and lun...

Pitfall of F-FDG PET/CT in Characterization of Relapsed Multisystem Lymphomatoid Granulomatosis.

We present serial F-FDG PET/CT findings in a case of Epstein-Barr virus positive pulmonary lymphomatoid granulomatosis, grade 3. The patient experienced transient complete response to R-CHOP chemother...

A rare endoscopic appearance of granulomatosis with polyangiitis involving the intestine: a case report.

The involvement of granulomatosis with polyangiitis is less frequent in the intestine.

Medical and Biotech [MESH] Definitions

A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and kidneys. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against neutrophil proteinase-3 (WEGENER AUTOANTIGEN).

A condition that is characterized by inflammation, ulceration, and perforation of the nose and the PALATE with progressive destruction of midline facial structures. This syndrome can be manifested in several diseases including the nasal type of EXTRANODAL NK-T-CELL LYMPHOMA and WEGENER GRANULOMATOSIS.

Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for WEGENER GRANULOMATOSIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.

A condition characterized by persistent or recurrent labial enlargement, ORAL ULCER, and other orofacial manifestations in the absence of identifiable CROHN DISEASE; or SARCOIDOSIS. There is no consensus on whether orofacial granulomatosis is a distinct clinical disorder or an initial presentation of Crohn disease.

An angiocentric and angiodestructive lymphoproliferative disorder primarily involving the lungs. It is caused by an Epstein-Barr virus-induced transformation of the B-cells, in a T-cell rich environment. Clinically and pathologically it resembles EXTRANODAL NK-T-CELL LYMPHOMA.

More From BioPortfolio on "Daclizumab to Treat Wegener's Granulomatosis"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...


Searches Linking to this Trial