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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 December 2017
Main ID:  NCT00076752
Date of registration: 02/02/2004
Prospective Registration: Yes
Primary sponsor: National Cancer Institute (NCI)
Public title: Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus
Scientific title: A Pilot Study of Intensified Lymphodepletion Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Systemic Lupus Erythematosus
Date of first enrolment: January 30, 2004
Target sample size: 9
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT00076752
Study type:  Interventional
Study design:  Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Contacts
Name:     Steven Pavletic, M.D.
Address: 
Telephone:
Email:
Affiliation:  National Cancer Institute (NCI)
Key inclusion & exclusion criteria

-INCLUSION CRITERIA

1. Age 15-40 years

2. Must fulfill at least 4 of the following 11 criteria for systemic lupus erythematous
(SLE) as defined by the American College of Rheumatology:

-Malar rash. Fixed erythema, flat or raised, over the malar eminences, tending to
spare the nasolabial folds.

- Discoid rash. Erythematous raised patches with adherent keratotic scaling and
follicular plugging; atrophic scarring may occur in older lesions.

- Photosensitivity. Skin rash as a result of unusual reaction to sunlight, by
patient history or physician observation.

- Oral ulcers. Oral or nasopharyngeal ulcerations, usually painless, observed by a
physician.

- Arthritis. Nonerosive arthritis involving two or more peripheral joints,
characterized by tenderness, swelling, or effusion.

- Serositis. a.) Pleuritis - convincing history of pleuritic pain or rub heard by a
physician or evidence of pleural effusion

OR

b.) Pericarditis - documented by electrocardiogram (ECG) or rub or evidence of
pericardial effusion

-Renal disorder. a.) Persistent proteinuria greater than 0.5 grams per day or greater
than 3+ if quantitation not performed

OR

b.) Cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed.

- Neurologic disorder. a.) Seizures - in the absence of offending drugs or known
metabolic derangements; eg, uremia, ketoacidosis, or electrolyte imbalance

OR

b.) Psychosis - in the absence of offending drugs or known metabolic derangements; eg,
uremia, ketoacidosis, or electrolyte imbalance

-Hematologic disorder. a.) Hemolytic anemia - with reticulocytosis

OR

b.) Leukopenia - less than 4000/ L total on two or more occasions

OR

c.) Lymphopenia - less than 1500/ L on two or more occasions

OR

d.) Thrombocytopenia - less than 100,000/ L in the absence of offending drugs

- Immunologic disorder. a.) Anti-deoxyribonucleic acid (DNA): antibody to native
DNA in abnormal titer

OR

b.) Anti-SM: presence of antibody to SM nuclear antigen

OR

c.) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum
level of immunoglobulin G (IgG) or immunoglobulin M (IgM) anti-cardiolipin antibodies,
(2) a positive test result for lupus anticoagulant using a standard method, or (3)
false positive serologic test for syphilis known to be positive for at least 6 months
and confirmed by Treponema Pallidum immobilization or fluorescent treponemal antibody
absorption test

-Antinuclear antibodies. An abnormal titer of ANAs by immunofluorescence or an
equivalent assay at any point in time in the absence of drugs known to be associated
with drug-induced lupus syndrome.

3. Have severe and active lupus, refractory to immunosuppressive therapy, defined as one
of the following (a-d):

a.Nephritis: Biopsy proven Diffuse Proliferative Glomerulonephritis (World Health
Organization (WHO) Class IV) with or without superimposed membranous changes

i.Active disease:

1. A kidney biopsy within three months of enrollment showing active WHO Class IV disease.
Activity will be determined based on the presence of endocapillary cellular
proliferation compromising the capillary loops or cellular crescents or necrosis on
light microscopy or subendothelial deposits on electron microscopy.

2. If a biopsy is contraindicated patients can be enrolled if they had a previous biopsy
showing Diffuse Proliferative Glomerulonephritis (WHO Class IV) and at the time of
enrollment have all of the following:

1. Proteinuria greater than 1gm/day

2. Active urine sediment defined as hematuria (greater than 10 red blood cell
(RBC)/hpf (high power field) on a nephrology urinalysis of a 50 mL urine sample)
with dysmorphic RBC and/or cellular casts on a nephrology urinalysis of a 50 mL
urine sample

3. Low C3 (less than 69 mg/dL) and/or elevated dsDNA antibodies (greater than 25EU)

3. Need for prednisone greater than 20 mg/day due to increased renal activity after at
least 6 months of cyclophosphamide.

ii. Treatment resistant:

1. Patients with active disease after at least 6 months of intravenous pulse
cyclophosphamide +/- iv methylprednisolone and daily oral prednisone, or

2. Early flare: those who have reactivation of their nephritis during or within 6 months
of completing cyclophosphamide therapy

3. Recalcitrant disease: two or more recurrences of lupus nephritis within five years of
enrollment. All flares must have received adequate therapy and least one of the
episodes must have been treated with minimum 6 months of intravenous pulse
cyclophosphamide plus iv methylprednisolone and maintenance oral prednisone.

Central nervous system (CNS) lupus: Lupus CNS manifestations indicative of
encephalitis or myelitis or vasculitis. Concomitant CNS diseases should be excluded.
(e.g. infections, multiple sclerosis; patients fulfilling multiple sclerosis (MS) and
SLE criteria will be excluded). Clinical signs and symptoms must be supported by
objective findings of CNS inflammation.

i. Active disease:

Signs/symptoms that are accepted for disease activity:

-Clinical signs and symptoms compatible with focal CNS damage -Severe global
neurocognitive/psychiatric impairment (eg: psychosis, organic brain syndrome, severe
depression)

-Intractable seizures

Clinical findings must be supported by at least one of the following:

1. Magnetic resonance imaging (MRI) findings consistent with transverse myelitis or

Central nervous system (CNS) vasculitis

- Signs of inflammation on MRI are either the presence of Gadolinium
(Gd)-enhancing lesions, or the increase of the number and/or volume of
T2-weighted lesions (or lesions showing up on fluid attenuated inversion recovery
(FLAIR) imaging). We will use the standard MS protocol sequences, which are
routinely used in the Clinical Center to evaluate inflammatory CNS lesions.

2. If patient has seizures/psychiatric signs and symptoms in the absence of clear
signs of vasculitis or cerebritis by MRI, the cerebral spinal fluid (CSF) should
show protein elevation above normal levels and abnorma



Age minimum: 15 Years
Age maximum: 40 Years
Gender: All
Health Condition(s) or Problem(s) studied
Lupus Erythematosus, Systemic
Intervention(s)
Biological: filgrastim
Biological: Rituxan (rituximab)
Drug: cyclophosphamide
Drug: Diphenhydramine
Drug: fludarabine phosphate
Drug: Mesna
Drug: methylprednisolone
Other: immunologic technique
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
Primary Outcome(s)
Relapse-free Complete Clinical Response [Time Frame: 60 months]
Secondary Outcome(s)
Absolute Lymphocyte Count [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Absolute Neutrophil Count [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Anti-Double Stranded Deoxyribonucleic Acid (DNA) Antibody [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Anti-Nuclear Antibody [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Anti-Smith-Ribonuclear Protein Antibody [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months and 2 years.]
Cluster of Differentiation 19 (CD19) + Cells [Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.]
Cluster of Differentiation 3 (CD3) + Cells [Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.]
Cluster of Differentiation 4 (CD4) + Cells [Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.]
Cluster of Differentiation 8 (CD8) + Cells [Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.]
Extractable Nuclear Antigen (ENA) [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Natural Killer Cells [Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years.]
Number of Participants With Adverse Events [Time Frame: 18 months]
Platelet Count [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [Time Frame: Day -7, day 0, 1 month, 3 months, 6 months, 1 year, 18 months, 2 years and 3 years.]
White Blood Cells [Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years.]
Secondary ID(s)
04-C-0095
040095
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available: Yes
Date Posted: 10/06/2014
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT00076752
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