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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00230035
• Date of registration: 28/09/2005
• Prospective Registration: No
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Lupus Immunosuppressive/Immunomodulatory Therapy or Stem Cell Transplant (LIST)
• Scientific 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
• Date of first enrolment: September 2005
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT00230035
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Betty Diamond, MD
• Affiliation: Department of Medicine, Columbia University

• Name: Ann Traynor, MD
• Affiliation: Division of Hematology and Oncology, University of Massachusetts Medical School

• Name: Richard Burt, MD
• Affiliation: Division of Immunotherapy, Northwestern University

• Name: Kenneth Kalunian, MD
• Affiliation: Division of Rheumatology, Allergy, and Immunology, University of California, Los Angeles

• Name: Bevra Hahn, MD
• Affiliation: Division of Rheumatology, Department of Medicine, University of California, Los Angeles

• Name: Keith Sullivan, MD
• Affiliation: Division of Cellular Therapy, Department of Medicine, Duke University

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Growth colony stimulating factor (G-CSF)

Procedure: Autologous CD34+HPC transplantation (HSCT)

Drug: Intravenous immunoglobulin

Drug: Rabbit anti-thymocyte globulin

Drug: Azathioprine

Drug: Leflunomide

Drug: Rituximab

Procedure: Leukapheresis

Drug: Corticosteroids

Drug: Methylprednisolone

Procedure: Plasmapheresis

Drug: Methotrexate

Drug: Mycophenolate mofetil

Procedure: Non-myeloablative high dose immunosuppressive therapy conditioning (HDIT)

Primary Outcome(s)

Mortality resulting from treatment, underlying disease, or unrelated causes [Time Frame: At Month 30]

Secondary ID(s)

DAIT SCSLE-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors