Lupus Immunosuppressive/Immunomodulatory Therapy or Stem Cell Transplant (LIST)

Summary

Systemic lupus erythematosus, also known as lupus or SLE, is a chronic, multisystem, autoimmune disease in which the body's internal system of defense attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, especially the skin, joints, lungs, heart, brain, intestines, and kidneys. Both genetic and environmental risk factors are involved in the development of lupus, but these are poorly understood.

SLE has an overall 10-year survival between 80 and 90%. However, we estimate that severe lupus not responding to the usual available treatments has a 50% mortality rate in 10 years. Kidney problems occur in 30% to 50% of lupus patients and may progress to kidney failure. Kidney disease due to lupus occurs more frequently in African-Americans and Hispanics. Lupus can affect many parts of the body and cause damage, but the severe form can result in death from kidney disease; cardiovascular disease, specifically atherosclerosis; central nervous system disease; and infections.

Currently, no single standard therapy for treatment of severe SLE exists. Usually physicians prescribe an aggressive regimen of one or a combination of immunosuppressive/immunomodulatory treatments. This approach to therapy for all forms of severe SLE derives largely from studies of lupus nephritis. Current treatment, although effective in many people, are not effective in all patients and are associated with drug-induced morbidity. The design of the control arm for this study reflects the current status of treatment of SLE in the academic setting. Investigators may choose from a list of commonly used and currently available immunosuppressive/immunomodulatory treatments to optimize the treatment of their patients, based on their past treatment history and response to those treatments. Study treatments may consist of corticosteroids, cyclophosphamide (CTX), azathioprine, methotrexate, cyclosporine, mycophenolate mofetil (MMF), plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and leflunomide. Treatment may be changed as frequently and as necessary within the first year of the study to control the manifestations of SLE in each patient. New therapies that become available during the course of this trial may be added to the list of approved medications for this study.

In response to the absence of a uniformly effective treatment for severe lupus, autologous hematopoietic stem cell transplantation (HSCT) has been proposed as a potential therapy. Hematopoietic stem cells are immature blood cells that can develop into all of the different blood and immune cells the body uses. Researchers believe that resetting the immune system may stop or slow down the progression of the disease. The main purpose of this study is to compare two ways of treating SLE: 1) high-dose immunosuppressive therapy (HDIT) followed by HSCT and 2) currently available immunosuppressive/immunomodulatory therapies.

Conditions

• Systemic Lupus Erythematosus

Interventions

PROCEDURE

Leukapheresis

PROCEDURE

Non-myeloablative high dose immunosuppressive therapy conditioning (HDIT)

PROCEDURE

Autologous CD34+HPC transplantation (HSCT)

PROCEDURE

Plasmapheresis

DRUG

Rabbit anti-thymocyte globulin

DRUG

Methylprednisolone

DRUG

Growth colony stimulating factor (G-CSF)

DRUG

Corticosteroids

DRUG

Mycophenolate mofetil

DRUG

Azathioprine

DRUG

Intravenous immunoglobulin

DRUG

Methotrexate

DRUG

Rituximab

DRUG

Leflunomide

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Richard Burt, MD · Division of Immunotherapy, Northwestern University

• Bevra Hahn, MD · Division of Rheumatology, Department of Medicine, University of California, Los Angeles

• Kenneth Kalunian, MD · Division of Rheumatology, Allergy, and Immunology, University of California, Los Angeles

• Ann Traynor, MD · Division of Hematology and Oncology, University of Massachusetts Medical School

• Keith Sullivan, MD · Division of Cellular Therapy, Department of Medicine, Duke University

• Betty Diamond, MD · Department of Medicine, Columbia University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-09-30

Countries

• United States

Study Locations