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NCT00076752

Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus

Completed Phase 2 Results posted Last updated 5 January 2021
What this trial tests

Phase 2 trial testing fludarabine phosphate in Lupus Erythematosus, Systemic in 9 participants. Completed in 15 October 2013.

Timeline
30 January 2004
Primary endpoint
15 October 2013
15 October 2013

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment9
Start date30 January 2004
Primary completion15 October 2013
Estimated completion15 October 2013
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 15 to 40, any sex, with Lupus Erythematosus, Systemic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Relapse-free Complete Clinical Response Primary · 60 months

Complete clinical response is defined as complete clinical response in the target organ and no clinical signs of active lupus as determined by a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of ≤3; prednisone ≤10mg/day at 6 months and ≤5mg/day at 12 months or later.

GroupValue95% CI
Autologous HSCT in SLE5436 – 60
Number of Participants With Adverse Events Secondary · 18 months

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

GroupValue95% CI
Autologous HSCT in SLE8
Anti-Nuclear Antibody Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

Anti-Nuclear antibody is a well accepted biological clinical laboratory marker of systemic lupus. Range of normal values is 0-0.9 EU.

Day -7
GroupValue95% CI
Autologous HSCT in SLE5.4± 4.65
Day 0
GroupValue95% CI
Autologous HSCT in SLE4.7± 4.73
1 month
GroupValue95% CI
Autologous HSCT in SLE3.7± 3.89
3 months
GroupValue95% CI
Autologous HSCT in SLE3.2± 3.91
6 months
GroupValue95% CI
Autologous HSCT in SLE2.7± 3.01
1 year
GroupValue95% CI
Autologous HSCT in SLE2.6± 2.77
18 months
GroupValue95% CI
Autologous HSCT in SLE2.8± 2.7
2 years
GroupValue95% CI
Autologous HSCT in SLE2.5± 2.59
Extractable Nuclear Antigen (ENA) Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

Extractable nuclear antigen is a well accepted biological clinical laboratory marker of systemic lupus. Range of normal values is 0-19.

Day -7
GroupValue95% CI
Autologous HSCT in SLE66.9± 74.48
Day 0
GroupValue95% CI
Autologous HSCT in SLE64.8± 70.61
1 month
GroupValue95% CI
Autologous HSCT in SLE61.5± 73.72
3 months
GroupValue95% CI
Autologous HSCT in SLE58.5± 67.03
6 months
GroupValue95% CI
Autologous HSCT in SLE51.3± 57.22
1 year
GroupValue95% CI
Autologous HSCT in SLE57.2± 58.07
18 months
GroupValue95% CI
Autologous HSCT in SLE60.6± 60.76
2 years
GroupValue95% CI
Autologous HSCT in SLE50.6± 49.04
Anti-Double Stranded Deoxyribonucleic Acid (DNA) Antibody Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

Anti-Double stranded deoxyribonucleic acid antibody is a well accepted biological clinical laboratory marker especially specific for systemic lupus. Range of normal values is 0-24 IU.

Day -7
GroupValue95% CI
Autologous HSCT in SLE17.3± 24.92
Day 0
GroupValue95% CI
Autologous HSCT in SLE8.8± 16.8
1 month
GroupValue95% CI
Autologous HSCT in SLE0± 0
3 months
GroupValue95% CI
Autologous HSCT in SLE0± 0
6 months
GroupValue95% CI
Autologous HSCT in SLE0± 0
1 year
GroupValue95% CI
Autologous HSCT in SLE0± 0
18 months
GroupValue95% CI
Autologous HSCT in SLE0± 0
2 years
GroupValue95% CI
Autologous HSCT in SLE0± 0
Anti-Smith-Ribonuclear Protein Antibody Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months and 2 years.

Anti-Smith-Ribonuclear protein antibody is a well accepted biological clinical laboratory marker of systemic lupus.Range of normal values is 0-19 EU.

Day -7
GroupValue95% CI
Autologous HSCT in SLE49± 49.51
Day 0
GroupValue95% CI
Autologous HSCT in SLE51.6± 53.72
1 month
GroupValue95% CI
Autologous HSCT in SLE31.5± 40.31
3 months
GroupValue95% CI
Autologous HSCT in SLE29.8± 41.48
6 months
GroupValue95% CI
Autologous HSCT in SLE28.5± 40.07
1 year
GroupValue95% CI
Autologous HSCT in SLE20± 34.64
18 months
GroupValue95% CI
Autologous HSCT in SLE16.67± 28.87
2 years
GroupValue95% CI
Autologous HSCT in SLE25.67± 44.46
White Blood Cells Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

The white blood cell test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 3.4-9.6 K/uL.

Day -7
GroupValue95% CI
Autologous HSCT in SLE6.89± 3.07
Day 0
GroupValue95% CI
Autologous HSCT in SLE0.47± 0.31
1 month
GroupValue95% CI
Autologous HSCT in SLE10.32± 6.6
3 months
GroupValue95% CI
Autologous HSCT in SLE3.84± 1.4
6 months
GroupValue95% CI
Autologous HSCT in SLE4.21± 1.38
1 year
GroupValue95% CI
Autologous HSCT in SLE5.81± 1.01
18 months
GroupValue95% CI
Autologous HSCT in SLE5.24± 0.82
2 years
GroupValue95% CI
Autologous HSCT in SLE7.17± 3.93
Absolute Neutrophil Count Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

The absolute neutrophil count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 1.29-7.5 K/uL.

Day -7
GroupValue95% CI
Autologous HSCT in SLE5.66± 2.88
Day 0
GroupValue95% CI
Autologous HSCT in SLE0.45± 0.3
1 month
GroupValue95% CI
Autologous HSCT in SLE9.11± 6.67
3 months
GroupValue95% CI
Autologous HSCT in SLE2.72± 0.93
6 months
GroupValue95% CI
Autologous HSCT in SLE2.78± 1.38
1 year
GroupValue95% CI
Autologous HSCT in SLE3.44± 0.97
18 months
GroupValue95% CI
Autologous HSCT in SLE2.72± 1.04
2 years
GroupValue95% CI
Autologous HSCT in SLE4.04± 1.7
Absolute Lymphocyte Count Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

The absolute lymphocyte count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 0.45-4.9 K/uL.

Day -7
GroupValue95% CI
Autologous HSCT in SLE0.54± 0.4
Day 0
GroupValue95% CI
Autologous HSCT in SLE0.0065± 0.0064
1 month
GroupValue95% CI
Autologous HSCT in SLE0.42± 0.18
3 months
GroupValue95% CI
Autologous HSCT in SLE0.53± 0.46
6 months
GroupValue95% CI
Autologous HSCT in SLE0.82± 0.31
1 year
GroupValue95% CI
Autologous HSCT in SLE1.75± 0.64
18 months
GroupValue95% CI
Autologous HSCT in SLE1.8± 0.61
2 years
GroupValue95% CI
Autologous HSCT in SLE1.8± 0.84
Platelet Count Secondary · Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.

The platelet count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 162-380 K/uL.

Day -7
GroupValue95% CI
Autologous HSCT in SLE251± 62.9
Day 0
GroupValue95% CI
Autologous HSCT in SLE113± 49
1 month
GroupValue95% CI
Autologous HSCT in SLE166± 61.6
3 months
GroupValue95% CI
Autologous HSCT in SLE187± 95.4
6 months
GroupValue95% CI
Autologous HSCT in SLE170± 64
1 year
GroupValue95% CI
Autologous HSCT in SLE226± 47.9
18 months
GroupValue95% CI
Autologous HSCT in SLE210± 43.5
2 years
GroupValue95% CI
Autologous HSCT in SLE308± 251.5
Cluster of Differentiation 3 (CD3) + Cells Secondary · Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.

The CD3+Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 650-2108 uL.

Day 0
GroupValue95% CI
Autologous HSCT in SLE2.99± 3.25
1 month
GroupValue95% CI
Autologous HSCT in SLE239.47± 210.74
3 months
GroupValue95% CI
Autologous HSCT in SLE435.97± 335.69
6 months
GroupValue95% CI
Autologous HSCT in SLE699.47± 256.67
1 year
GroupValue95% CI
Autologous HSCT in SLE1493.29± 605.26
2 years
GroupValue95% CI
Autologous HSCT in SLE1678.76± 888.41
Cluster of Differentiation 4 (CD4) + Cells Secondary · Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.

The CD4 + Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 358-1259 uL.

Day 0
GroupValue95% CI
Autologous HSCT in SLE2.58± 2.98
1 month
GroupValue95% CI
Autologous HSCT in SLE103.37± 117.43
3 months
GroupValue95% CI
Autologous HSCT in SLE112.8± 101.94
6 months
GroupValue95% CI
Autologous HSCT in SLE316.25± 193.01
1 year
GroupValue95% CI
Autologous HSCT in SLE702.87± 362.75
2 years
GroupValue95% CI
Autologous HSCT in SLE958.03± 735.04

Adverse events — posted to ClinicalTrials.gov

Time frame: 18 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Autologous HSCT in SLE
Serious: 8/9 (89%)
Deaths: 2/9

Serious adverse events (16 terms)

ReactionSystemAutologous HSCT in SLE
hypoxiaRespiratory, thoracic and mediastinal disorders
Death Not Associated with CTCAE term: Death NOSGeneral disorders
allergic reaction/hypersensitivity (including drug fever)Immune system disorders
conduction abnormality/atrioventricular heart block: asystoleCardiac disorders
hypertensionCardiac disorders
gastrointestinal-Other (Specify)Gastrointestinal disorders
infectionInfections and infestations
infection - Other (Specify, CMV antigenemia without neutropenia)Infections and infestations
ALT/SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
AST/SGOT (serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
potassium, serum-high (hyperkalemia)Metabolism and nutrition disorders
sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
encephalopathyNervous system disorders
hydrocephalusNervous system disorders
neuropathy: motorNervous system disorders
neuropathy: sensoryNervous system disorders
Other adverse events (124 terms — click to expand)

ReactionSystemAutologous HSCT in SLE
HemoglobinBlood and lymphatic system disorders
Leukocytes (total WBC)Blood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders
PlateletsBlood and lymphatic system disorders
Calcium, serum-low (hypocalcemia)Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)Metabolism and nutrition disorders
NauseaGastrointestinal disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders
Potassium, serum-high (hyperkalemia)Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders
Pain:: BackMusculoskeletal and connective tissue disorders
Pain:: BoneMusculoskeletal and connective tissue disorders
Pain:: Head/headacheNervous system disorders
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders
HypotensionCardiac disorders
PTT (Partial Thromboplastin Time)Blood and lymphatic system disorders
DiarrheaGastrointestinal disorders
VomitingGastrointestinal disorders
Infection with normal ANC or Grade 1 or 2 neutrophils:: BloodInfections and infestations
Alkaline phosphataseMetabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
Vision-blurred visionEye disorders
Pain:: Chest/thorax NOSMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)Respiratory, thoracic and mediastinal disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)General disorders
Hair loss/alopecia (scalp or body)Skin and subcutaneous tissue disorders
Febrile neutropeniaInfections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils:: Urinary tract NOSInfections and infestations
AmylaseMetabolism and nutrition disorders
Bicarbonate, serum-lowMetabolism and nutrition disorders
CreatinineMetabolism and nutrition disorders
HemoglobinuriaMetabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)Metabolism and nutrition disorders

Most-reported serious reactions: hypoxia, Death Not Associated with CTCAE term: Death NOS, allergic reaction/hypersensitivity (including drug fever), conduction abnormality/atrioventricular heart block: asystole, hypertension, gastrointestinal-Other (Specify), infection, infection - Other (Specify, CMV antigenemia without neutropenia).

Data from ClinicalTrials.gov NCT00076752 adverse events section.

Sponsor's own description

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. ...

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics.
    Dai X, Fan Y, Zhao X. · · 2025 · cited 78× · PMID 40097390 · DOI 10.1038/s41392-025-02168-0
  2. Use of a novel virus detection assay to identify coronavirus HKU1 in the lungs of a hematopoietic stem cell transplant recipient with fatal pneumonia.
    Uhlenhaut C, Cohen JI, Pavletic S, Illei G, et al · · 2012 · cited 21× · PMID 21749586 · DOI 10.1111/j.1399-3062.2011.00657.x
  3. Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus.
    Goklemez S, Hasni S, Hakim FT, Muraro PA, et al · · 2022 · cited 19× · PMID 34875023 · DOI 10.1093/rheumatology/keab877
  4. Advances in hematopoietic stem cell transplantation for autoimmune diseases.
    Xu Y, Wang X, Hu Z, Huang R, et al · · 2024 · cited 4× · PMID 39492896 · DOI 10.1016/j.heliyon.2024.e39302
  5. Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.
    Natoli V, Charras A, Smith EM, Hedrich CM. · · 2025 · cited 1× · PMID 41410901 · DOI 10.1007/s11926-025-01207-7
  6. Tissue regenerative medicine: Clinical advances, challenges, and opportunities.
    Badawy S, Gopinath V, Espinosa AMD, Suthiwanich K, et al · · 2025 · PMID 41424914 · DOI 10.1063/5.0296897
  7. Stem Cell Therapy in the Treatment of Rheumatic Diseases and Application in the Treatment of Systemic Lupus Erythematosus
    Leung P, Shuai Z, Liu B, Shu S, et al · · 2016

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00076752.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing