Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus
Drug: intravenous immunoglobulin
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2 Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus|
- clinical outcome: extent and severity of disease [ Time Frame: 6 - 10 weeks after initiation of therapy ] [ Designated as safety issue: No ]
- serum levels of pemphigus antibodies [ Time Frame: 6-10 weeks after initiation of therapy ] [ Designated as safety issue: No ]
- toxicity of treatment: measured in renal toxicity, myelosuppression or hepatic toxicity [ Time Frame: Throughout course of study ] [ Designated as safety issue: Yes ]
- ability to be weaned off steroids [ Time Frame: Measured 6 and 10 weeks after initiation of IVIg treatment ] [ Designated as safety issue: No ]
|Study Start Date:||April 2007|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Group A
Drug: intravenous immunoglobulin
Gamunex 10% 500/mg/kg/day x four days per cycle total of four cycles
Experimental: Group B
IVIg with cyclophosphamide
cyclophosphamide dose of 2mg/kg/day divided into three-times daily oral administration
Pemphigus is a serious and life-threatening autoimmune disease characterized by blisters and erosions that occur on the skin and oral mucosa. It is caused by autoantibodies that attack desmoglein 1 and 3, adhesion molecules that are present on the surface of the cells (keratinocytes) that make up the superficial layer of the skin. As a result these cells stop sticking together, and come apart resulting in the formation of blisters on the skin.
Pemphigus is usually treated with systemic corticosteroids often given together with immunosuppressive drugs such as Cytoxan (cyclophosphamide), Imuran (azathioprine), methotrexate, CellCept (mycophenolate mofetil) and others. However, the prolonged and high doses of systemic steroids and other immunosuppressive agents used to treat the disease are associated with significant toxicity.
A new treatment which is now being used to treat pemphigus patients that are unresponsive, or that have developed complications to conventional treatment is IVIg. IVIg consists of one of the protein fractions present in blood. It is the fraction that contains antibodies and is called immunoglobulin (Ig). It is purified from blood that has been collected from thousands of donors and treated to remove potential infectious agents. It is administered intravenously (IV) over several hours, several days in succession. The cycles are usually repeated every 2 to 4 weeks until the disease is controlled.
IVIg treatment is currently given in either of two ways, either by itself or with an immunosuppressive drug such as cyclophosphamide or azathioprine. It is unknown which of these two procedures is better. This trial is being conducted to determine which treatment is more effective.
The trial is being conducted in patients with pemphigus that are not responding to, or have developed complications from, standard treatment. All patients will be treated with IVIg administered using a standard protocol. The IVIg will be given daily for 4 days, and this cycle will be repeated every other week for a total of 4 cycles. In addition, half of the patients will be selected by chance to also be treated with cyclophosphamide, an immunosuppressive drug often used to treat other autoimmune diseases including pemphigus. The cyclophosphamide is a pill that is taken 3 times a day. A total of 12 patients will be treated in each arm of the trial. The trial is being conducted by Dr. Jean-Claude Bystryn at the New York University Medical Center.
The extent and activity of the disease, as well as the blood levels of pemphigus antibodies, will be measured at baseline prior to entry into the trial and periodically during the trial.
The goal of the study is to determine whether there is a difference between the two treatments in the rate at which: 1) the activity and extent of the disease improves, 2) the dose of corticosteroids required to treat the disease can be reduced, and 3) the blood level of pemphigus antibodies decrease.
This trial will test this hypothesis by examining whether IVIg treatment given with cyclophosphamide results in a more rapid decline in circulating pemphigus antibodies than when given alone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00483119
|United States, New York|
|NYU Medical Center|
|New York, New York, United States, 10016|
|Principal Investigator:||Jean-Claude Bystryn, M.D.||NYU MEDICAL CENTER|