Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus

This study has been terminated.
(Study was terminated due to the death of the PI.)
Sponsor:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00483119
First received: June 5, 2007
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to compare two standard treatments for pemphigus to determine which more effectively improves the clinical manifestations of the disease and decreases serum level of the autoantibodies which cause the disease.


Condition Intervention Phase
Pemphigus Vulgaris
Drug: intravenous immunoglobulin
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: April 2007
Study Completion Date: February 2011
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A
IVIg alone
Drug: intravenous immunoglobulin
Gamunex 10% 500/mg/kg/day x four days per cycle total of four cycles
Experimental: Group B
IVIg with cyclophosphamide
Drug: cyclophosphamide
cyclophosphamide dose of 2mg/kg/day divided into three-times daily oral administration

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Lesions consistent with pemphigus foliaceus or vulgaris
  • Diagnosis confirmed by histology and IIF ≥ 40 within past month
  • On ≥20mg/day of prednisone per day for two weeks or ≥ 80mg/day for one week
  • Women of childbearing potential negative HCG obtained two weeks prior to first IVIg
  • Agrees to two acceptable forms of contraception* if randomized to cyclophosphamide group:
  • IUD (except progesterone T), Combination oral contraceptives, transdermal patch, vaginal ring, hormonal injectables or implantables, male latex condom, diaphragm, cervical cap, or vaginal sponge (contains spermicide)
  • Normal organ function confirmed by CBC, UA, LFTs and Ig levels within defined inclusion criteria
  • Responds yes to at least one of the criteria below:
  • Persistence of clinical manifestations of disease despite steroid treatment
  • Flare in disease activity after an attempt at steroid tapering
  • Failure of established lesions to heal
  • Rapidly progressive disease.
  • Conventional therapy is relatively contraindicated i.e. side effects, co-morbid conditions
  • systemic infections, peptic ulcers, osteoporosis, hypertension, cataracts or others

Exclusion Criteria:

  • Use of IVIg within past 3 weeks or the use of a cytotoxic drug within the past 2 weeks
  • Participating in another clinical trial at the time of screening and enrollment
  • Medical condition that precludes use of IVIg or cyclophosphamide (i.e. pregnancy breastfeeding, underlying chronic infection, concurrent opportunistic infection, sepsis or volume depletion
  • Renal insufficiency ( GFR <90, proteinuria (>1+, x 2), creatinine >1.8 or increased WBC or RBCs which cannot be explained by cystitis.)
  • Known hypersensitivity to study drugs, IVIg or cyclophosphamide
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00483119

Locations
United States, New York
NYU Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Jean-Claude Bystryn, M.D. NYU MEDICAL CENTER
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00483119     History of Changes
Other Study ID Numbers: 3343
Study First Received: June 5, 2007
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
pemphigus vulgaris
IVIg
cyclophosphamide
treatment
pemphigus antibodies

Additional relevant MeSH terms:
Pemphigus
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014