Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus
Status:
Completed
Trial end date:
2013-10-15
Target enrollment:
Participant gender:
Summary
This study will examine a new approach to treating patients with severe systemic lupus
erythematosus (SLE) that involves collecting stem cells (cells produced by the bone marrow
that develop into blood cells) from the patient, completely shutting down the patient's
immune system, and then giving back the patient's stem cells. SLE is a chronic, inflammatory
disorder of the immune system that can affect many organs. It is called an autoimmune disease
because the patient's lymphocytes (white blood cells that normally protect against invading
organisms), go out of control and attack the body's own tissues.
Patients between 15 and 40 years of age with severe SLE affecting a major organ that is
resistant to standard treatment may be eligible for this study. Candidates are screened with
a medical history and physical examination, blood and urine tests, skin tuberculin test, and
radiology studies to evaluate the extent of disease. They have endocrinology, nutrition,
dental, and social work consultations, ultrasound or MUGA (multi-gated acquisition scan) scan
heart imaging, electrocardiogram and lung function tests, bone marrow biopsy, and lymph node
aspirate. Depending on which organs are affected, patients may have additional tests, such as
lumbar puncture (spinal tap), kidney or lung biopsy, MRI (magnetic resonance imaging) of the
brain and spinal cord, and PET (positron emission tomography) scan. They also complete
quality of life questionnaires and have disability functional testing and neurocognitive
(thinking) assessments.
Participants have a central venous line (plastic tube) inserted into a neck or chest vein for
administering stem cells and medicines and for drawing blood. They undergo seven apheresis
procedures during the course of the study to collect stem cells for transplant and for
research. For apheresis, whole blood is collected through a needle in an arm vein and
directed to a cell-separating machine where the white cells are extracted and the rest of the
blood is returned to the patient through the same needle.
Patients are primed with three medications (methylprednisolone, rituximab, and
cyclophosphamide) through the central line to help control the disease. In addition, a
medication called G-CSF (growth colony stimulating factor) is injected under the skin for
several days to boost production of stem cells. After enough stem cells have been collected
for transplantation (infusion through the central line), patients are admitted to the
hospital for an 8-day conditioning regimen followed by transplantation. The conditioning
treatment consists of rituximab, fludarabine, and cyclophosphamide to eliminate all the white
blood cells from the blood and bone marrow. The stem cells are then infused and the patient
is closely monitored by a team of physicians and nurses. When the stem cells have engrafted,
the bone marrow has recovered, and the patient feels well enough - usually 2 to 3 weeks after
transplant - the patient is discharged from the hospital. Prednisone tapering begins as soon
as feasibly possible, but no later then 28 days after transplant.
Patients return to the National Institutes of Health (NIH) Clinical Center for frequent
follow-up visits during the first 2 to 3 months following transplant. The time between visits
is then extended to once every 3 months the first year, then every 6 months the second year,
and then at least yearly for 5 years after the transplant. These visits include a physical
examination, blood and urine tests, lumbar puncture (if there is central nervous system
involvement), other appropriate biopsies and tests as needed to monitor the patient's health,
short apheresis procedures to collect blood for research purposes, and quality of life
questionnaires. Some select procedures will be optional. Bone marrow biopsies and lymph node
aspirates are done at beginning and at 6, 12, and 24 months after transplant. PET scans are
done at 1, 6, 12, and 24 months.
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