At a glance
ClinicalIndex Comparison Record- ✓Age 15–40 years
- ✓Must fulfill at least 4 of 11 American College of Rheumatology SLE criteria (malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, or antinuclear antibodies)
- ✓Severe and active lupus refractory to immunosuppressive therapy, defined as: (a) Biopsy-proven Diffuse Proliferative Glomerulonephritis (WHO Class IV), or (b) CNS lupus with encephalitis/myelitis/vasculitis supported by objective findings, or (c) Active pneumonitis/alveolitis/vasculitis, or (d) Severe immune-mediated thrombocytopenia or anemia
- ✓For lupus nephritis: either kidney biopsy within 3 months showing active WHO Class IV disease, OR prior WHO Class IV biopsy with proteinuria >1 g/day, active urinary sediment (hematuria >10 RBC/hpf with dysmorphic RBC and/or casts), and low C3 (<69 mg/dL) and/or elevated dsDNA (>25 EU)
- ✕Pregnant or lactating women; women of childbearing potential must have negative pregnancy test at screening
- ✕Women of childbearing potential not practicing or unwilling to practice birth control during entire study; men unwilling to practice birth control for first 6 months after transplant
- ✕Evidence of infection with hepatitis B, hepatitis C, or HIV
- ✕History of malignancy other than basal cell carcinoma of the skin
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Pilot Study of Intensified Lymphodepletion Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Systemic Lupus Erythematosus
In Brief
A Phase 2 clinical trial evaluating fludarabine phosphate, cyclophosphamide, and 8 other interventions for Lupus Erythematosus, Systemic. Completed, enrolled 9 participants across 1 site.
Detailed 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. ...
Study Details
Timeline
Interventions
Conditioning and transplant regimen: 30 mg/m\^2 day intravenous infusion over 30 minutes daily, 4 days (transplant days -6, -5, -4, -3)
Priming regimen: 2000 mg/m\^2 intravenous infusion over 2 hours, day 2. Conditioning and transplant regimen: 1200 mg/m\^2 day intravenous infusion daily, 4 days (-6, -5, -4, -3).
Priming regimen: 375 mg/m\^2 intravenous day 1, 4. Conditioning and transplant regimen: 750 mg/m\^2 intravenous infusion, day -7.
Priming regimen: 10 micrograms/kg/day subcutaneous, starting day 6. Conditioning and transplant regimen: 5 micrograms/kg/day subcutaneous, day +1 until ANC \>500 microliters.
Priming regimen:1000 mg intravenous over 30 minutes, day 1.
Lymphoablative regimen using cyclophosphamide, rituximab, and fludarabine followed by a CD34 cell selected autologous stem cell transplant.
Standard human immunology research laboratory ex vivo studies.
Day 0, product will be infused rapidly intravenously after premedication with diphenhydramine 25-60 mg orally or intravenous.
Conditioning and transplant regimen 25-50 mg orally or intravenously.
Priming regimen: 600 mg/m\^2 intravenous immediately prior to cyclophosphamide and repeat at 4 and 7 hours after the first dose, day 2. Conditioning and transplant regimen:1200 mg/m\^2 per day continuous 24 hour intravenous infusion, daily for 4 days, start concurrently with the start of cyclophosphamide.