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

This study has been withdrawn prior to enrollment.
(Recommended by DSMB due to lack of accrual)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00230035
First received: September 28, 2005
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Systemic Lupus Erythematosus
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Phase II Multicenter Study of Non-Myeloablative Autologous Transplantation With Auto-CD34+HPC Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Mortality resulting from treatment, underlying disease, or unrelated causes [ Time Frame: At Month 30 ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: September 2005
Arms Assigned Interventions
Experimental: 1
high dose immunosuppressie therapy (HDIT) followed by HSCT (hemopoietic stem cell transplantation).
Procedure: Leukapheresis Procedure: Non-myeloablative high dose immunosuppressive therapy conditioning (HDIT) Procedure: Autologous CD34+HPC transplantation (HSCT)
Active Comparator: 2
Currently available immunosuppressive/immunomodulatory therapy
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects between the ages of 18 and 60 years, inclusive
  • Meet at least 4 of 11 American College of Rheumatology (ACR) Revised Classification Criteria for SLE
  • Have at least one of the following conditions defining severe steroid refractory disease:

    a) Lupus nephritis - Subjects must have severe disease, defined as meeting criteria for BILAG renal category A, and be corticosteroid dependent while receiving at least 6 months of pulse CTX at doses of 500 to 1000 mg/m2 every 4 weeks or MMF at of 2 g/day or greater. If nephritis is to constitute the sole eligibility, a renal biopsy performed within 11 months of the date of screening must show ISN/RPS 2003 classification of lupus nephritis Class III or IV disease. A renal biopsy must demonstrate the potential of a reversible (non-fibrotic) component. b) Visceral organ involvement other than nephritis - Subjects must be without mesenteric vasculitis. The subject must be BILAG cardiovascular/respiratory category A, vasculitis category A, or neurologic category A, and be corticosteroid dependent while receiving at least 3 months of oral (2 to 3 mg/kg/day or greater) or IV CTX (500 mg/m2 or greater every 4 weeks). c) Cytopenias that are immune-mediated - Subjects must be BILAG hematologic category A and be corticosteroid dependent while receiving at least one of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months, MMF at 2 g/day or greater for more than 3 months, CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day orally for at least 3 months, cyclosporine at 3 mg/kg/day or greater for at least 3 months, or have had a splenectomy. d) Mucocutaneous disease - Subjects must meet BILAG mucocutaneous category A and be corticosteroid dependent while receiving at least 1 of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months; methotrexate at 15 mg/week or greater for at least 3 months; CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day or greater orally for at least 3 months, cyclosporine at 3 mg/kg/day or greater for at least 3 months, or MMF at doses 2 g/day or greater for at least 3 months. e) Arthritis/myositis - Subjects must meet BILAG musculoskeletal category A and be corticosteroid dependent while receiving at least one of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months, methotrexate at 15 mg/week or greater for at least 3 months, CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day or greater orally for at least 3 months, MMF at 2 g/day or greater for at least 3 months, or cyclosporine at 3 mg/kg/day or greater for at least 3 months.

  • Have the ability and willingness to provide written informed consent. In case of lupus cerebritis, a person designated by the subject may give consent.
  • Must be ANA positive

Exclusion Criteria:

  • HIV positive status
  • Any active systemic infection
  • Hepatitis B surface antigen positive
  • Hepatitis C PCR positive
  • Use of immunosuppressive agents for other indications other than SLE
  • Any comorbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy
  • For lupus nephritis: renal biopsy, performed within 11 months of the screening date, showing Class I, II, or V disease or Class III or IV disease in conjunction with total sclerosis of 50% or more of the glomeruli
  • Ongoing cancer. Patients with localized basal cell or squamous skin cancer are not excluded.
  • Pregnancy, unwillingness to use acceptable means of birth control, or unwilling to accept or comprehend irreversible sterility as a side effect of therapy
  • Psychiatric illness or mental deficiency not due to active lupus cerebritis making compliance with treatment or informed consent impossible
  • Hemoglobin adjusted diffusion capacity test (DLCO) less than 30% at screening
  • Resting left ventricular ejection fraction (LVEF) 40% or less as evaluated by echocardiogram
  • History of an allergic reaction or hypersensitivity to Escherichia coli recombinant proteins, CTX, or any part of the investigative or control therapy
  • SGOT/SGPT greater than 2 x the upper limit of normal, unless due to active lupus
  • ANC 1000 or greater if not due to active SLE
  • Subdural hematoma or any active intracranial bleeding documented within 30 days of the screening visit
  • Failure to be approved for participation in this study by the SCSLE Protocol Eligibility Review Committee
  • Positive tuberculin skin test
  • Presence of mesenteric vasculitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00230035

Locations
United States, California
UCSD, Thornton Hospital
La Jolla, California, United States, 92037-0943
UCLA, Rehabilitation Center
Los Angeles, California, United States, 90095-1670
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, New York
Feinstein Institute for Medical Research NS-LIJ Health System
Manhassat, New York, United States, 11030
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27709
Sponsors and Collaborators
Investigators
Study Chair: Richard Burt, MD Division of Immunotherapy, Northwestern University
Study Chair: Bevra Hahn, MD Division of Rheumatology, Department of Medicine, University of California, Los Angeles
Study Chair: Kenneth Kalunian, MD Division of Rheumatology, Allergy, and Immunology, University of California, Los Angeles
Study Chair: Ann Traynor, MD Division of Hematology and Oncology, University of Massachusetts Medical School
Study Chair: Keith Sullivan, MD Division of Cellular Therapy, Department of Medicine, Duke University
Study Chair: Betty Diamond, MD Department of Medicine, Columbia University
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00230035     History of Changes
Other Study ID Numbers: DAIT SCSLE-01
Study First Received: September 28, 2005
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antilymphocyte Serum
Azathioprine
Immunoglobulins
Antibodies
Methotrexate
Mycophenolate mofetil
Leflunomide
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Rituximab
Immunosuppressive Agents
Methylprednisolone Hemisuccinate
Prednisolone
Mycophenolic Acid
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 21, 2014