Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus
This study will examine a new approach to treating patient 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 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 of the brain and spinal cord, and PET 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 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 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.
Lupus Erythematosus, Systemic
Drug: fludarabine phosphate
Biological: Rituxan (rituximab)
Other: immunologic technique
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Intensified Lymphodepletion Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Systemic Lupus Erythematosus|
- Continuous relapse-free complete clinical response at 24 months post-transplantation. [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Time to flare-free complete response [ Designated as safety issue: No ]
- Time to complete clinical response [ Designated as safety issue: No ]
- Time to partial response [ Designated as safety issue: No ]
- Time to relapse [ Designated as safety issue: No ]
- improvement in general disease activity measured by Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [ Designated as safety issue: No ]
- Time to normalization of dsDNA and complement levels [ Designated as safety issue: No ]
- Pain scale and quality of life [ Designated as safety issue: No ]
- Functional assessment by HAQ score, neurocognitive testing, and depression scale. [ Designated as safety issue: No ]
|Study Start Date:||January 2004|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
Drug: fludarabine phosphate
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Steven Z Pavletic, M.D.||National Cancer Institute (NCI)|